Trial of Prasinezumab in Early-Stage Parkinson's Disease.

Autor:	Pagano G; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Taylor KI; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Anzures-Cabrera J; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Marchesi M; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Simuni T; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Marek K; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Postuma RB; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Pavese N; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Stocchi F; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Azulay JP; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Mollenhauer B; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., López-Manzanares L; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Russell DS; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Boyd JT; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Nicholas AP; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Luquin MR; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Hauser RA; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Gasser T; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Poewe W; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Ricci B; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Boulay A; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Vogt A; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Boess FG; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Dukart J; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., D'Urso G; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Finch R; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Zanigni S; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Monnet A; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Pross N; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Hahn A; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Svoboda H; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Britschgi M; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Lipsmeier F; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Volkova-Volkmar E; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Lindemann M; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Dziadek S; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Holiga Š; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Rukina D; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Kustermann T; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Kerchner GA; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Fontoura P; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Umbricht D; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Doody R; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Nikolcheva T; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.)., Bonni A; From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.).
Jazyk:	angličtina
Zdroj:	The New England journal of medicine [N Engl J Med] 2022 Aug 04; Vol. 387 (5), pp. 421-432.
DOI:	10.1056/NEJMoa2202867
Abstrakt:	Background: Aggregated α-synuclein plays an important role in the pathogenesis of Parkinson's disease. The monoclonal antibody prasinezumab, directed at aggregated α-synuclein, is being studied for its effect on Parkinson's disease. Methods: In this phase 2 trial, we randomly assigned participants with early-stage Parkinson's disease in a 1:1:1 ratio to receive intravenous placebo or prasinezumab at a dose of 1500 mg or 4500 mg every 4 weeks for 52 weeks. The primary end point was the change from baseline to week 52 in the sum of scores on parts I, II, and III of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 236, with higher scores indicating greater impairment). Secondary end points included the dopamine transporter levels in the putamen of the hemisphere ipsilateral to the clinically more affected side of the body, as measured by 123 I-ioflupane single-photon-emission computed tomography (SPECT). Results: A total of 316 participants were enrolled; 105 were assigned to receive placebo, 105 to receive 1500 mg of prasinezumab, and 106 to receive 4500 mg of prasinezumab. The baseline mean MDS-UPDRS scores were 32.0 in the placebo group, 31.5 in the 1500-mg group, and 30.8 in the 4500-mg group, and mean (±SE) changes from baseline to 52 weeks were 9.4±1.2 in the placebo group, 7.4±1.2 in the 1500-mg group (difference vs. placebo, -2.0; 80% confidence interval [CI], -4.2 to 0.2; P = 0.24), and 8.8±1.2 in the 4500-mg group (difference vs. placebo, -0.6; 80% CI, -2.8 to 1.6; P = 0.72). There was no substantial difference between the active-treatment groups and the placebo group in dopamine transporter levels on SPECT. The results for most clinical secondary end points were similar in the active-treatment groups and the placebo group. Serious adverse events occurred in 6.7% of the participants in the 1500-mg group and in 7.5% of those in the 4500-mg group; infusion reactions occurred in 19.0% and 34.0%, respectively. Conclusions: Prasinezumab therapy had no meaningful effect on global or imaging measures of Parkinson's disease progression as compared with placebo and was associated with infusion reactions. (Funded by F. Hoffmann-La Roche and Prothena Biosciences; PASADENA ClinicalTrials.gov number, NCT03100149.). (Copyright © 2022 Massachusetts Medical Society.)
Databáze:	MEDLINE
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