Creating the Pick's disease International Consortium: Association study of MAPT H2 haplotype with risk of Pick's disease.

Autor:	Valentino RR; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA., Scotton WJ; Dementia Research Centre, Department of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, UK., Roemer SF; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA., Lashley T; Queen Square Brain Bank for Neurological Disorders, University College London, Queen Square Institute of Neurology London, UK.; Department of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, UK., Heckman MG; Division of Clinical Trials and Biostatistics, Mayo Clinic, Jacksonville, FL 32224, USA., Shoai M; Department of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, UK., Martinez-Carrasco A; Department of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology, London, UK., Tamvaka N; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA., Walton RL; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA., Baker MC; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA., Macpherson HL; Department of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, UK., Real R; Department of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology, London, UK., Soto-Beasley AI; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA., Mok K; Department of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, UK.; UK Dementia Research Institute at UCL, London, UK.; Division of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.; Hong Kong Center for Neurodegenerative Diseases, Hong Kong Science Park, Hong Kong, China., Revesz T; Queen Square Brain Bank for Neurological Disorders, University College London, Queen Square Institute of Neurology London, UK.; Department of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, UK., Warner TT; Queen Square Brain Bank for Neurological Disorders, University College London, Queen Square Institute of Neurology London, UK.; Department of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology, London, UK., Jaunmuktane Z; Queen Square Brain Bank for Neurological Disorders, University College London, Queen Square Institute of Neurology London, UK.; Department of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology, London, UK., Boeve BF; Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA., Christopher EA; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA., DeTure M; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA., Duara R; Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center Miami Beach, FL., Graff-Radford NR; Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA., Josephs KA; Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA., Knopman DS; Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA., Koga S; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA., Murray ME; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA., Lyons KE; University of Kansas Medical Center, Parkinson's Disease & Movement Disorder Division, Kansas City, KS. 66160., Pahwa R; University of Kansas Medical Center, Parkinson's Disease & Movement Disorder Division, Kansas City, KS. 66160., Parisi JE; Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA., Petersen RC; Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA., Whitwell J; Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA., Grinberg LT; Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA., Miller B; Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA., Schlereth A; Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA., Seeley WW; Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA., Spina S; Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA., Grossman M; Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA., Irwin DJ; Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA., Lee EB; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA., Suh E; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA., Trojanowski JQ; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA., Van Deerlin VM; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA., Wolk DA; Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA., Connors TR; Neuropathology Service, C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA., Dooley PM; Neuropathology Service, C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA., Frosch MP; Neuropathology Service, C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA., Oakley DH; Neuropathology Service, C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA., Aldecoa I; Pathology, BDC, Hospital Clinic de Barcelona, Barcelona, Spain.; University of Barcelona, Barcelona, Spain.; Neurological Tissue Bank, Biobanc-Hospital Clínic-FRCB-IDIBAPS, Barcelona, Spain., Balasa M; Alzheimer's Disease and other Cognitive Disorders Unit, Neurology Department, Hospital Clinic, Barcelona, Spain.; Barcelona Clinical Research Foundation-August Pi i Sunyer Biomedical Research Institute (FRCB-IDIBAPS), Barcelona, Spain., Gelpi E; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria., Borrego-Écija S; Alzheimer's Disease and other Cognitive Disorders Unit, Neurology Department, Hospital Clinic, Barcelona, Spain.; Barcelona Clinical Research Foundation-August Pi i Sunyer Biomedical Research Institute (FRCB-IDIBAPS), Barcelona, Spain.; University of Barcelona, Barcelona, Spain., de Eugenio Huélamo RM; Hospital de Palamós, Carrer Hospital, 36, 17230 Palamós, Girona, Spain., Gascon-Bayarri J; Servei de Neurologia, Hospital Universitari de Bellvitge. Institut d'Investigació Biomèdica de Bellvitge (Idibell). L'Hospitalet de Llobregat, Spain., Sánchez-Valle R; Alzheimer's Disease and other Cognitive Disorders Unit, Neurology Department, Hospital Clinic, Barcelona, Spain.; Barcelona Clinical Research Foundation-August Pi i Sunyer Biomedical Research Institute (FRCB-IDIBAPS), Barcelona, Spain.; University of Barcelona, Barcelona, Spain., Sanz-Cartagena P; Hospital de Mataro, Carr. de Cirera, 230, 08304 Mataró, Barcelona, Spain., Piñol-Ripoll G; Unitat Trastorns Cognitius (Cognitive Disorders Unit), Clinical Neuroscience Research, IRBLleida, Santa Maria University Hospital, Lleida, Spain., Molina-Porcel L; Neurological Tissue Bank, Biobanc-Hospital Clínic-FRCB-IDIBAPS, Barcelona, Spain.; Alzheimer's Disease and other Cognitive Disorders Unit, Neurology Department, Hospital Clinic, Barcelona, Spain.; Barcelona Clinical Research Foundation-August Pi i Sunyer Biomedical Research Institute (FRCB-IDIBAPS), Barcelona, Spain., Bigio EH; Mesulam Center for Cognitive Neurology & Alzheimer's Disease, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Flanagan ME; Mesulam Center for Cognitive Neurology & Alzheimer's Disease, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Gefen T; Mesulam Center for Cognitive Neurology & Alzheimer's Disease, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.; Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Rogalski EJ; Mesulam Center for Cognitive Neurology & Alzheimer's Disease, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.; Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Weintraub S; Mesulam Center for Cognitive Neurology & Alzheimer's Disease, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.; Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Redding-Ochoa J; Johns Hopkins School of Medicine, Baltimore, MD, USA., Chang K; Johns Hopkins School of Medicine, Baltimore, MD, USA., Troncoso JC; Johns Hopkins School of Medicine, Baltimore, MD, USA., Prokop S; Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, USA., Newell KL; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA., Ghetti B; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA., Jones M; Cerebral Function Unit, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, UK.; Division of Neuroscience, School of Biological Sciences, University of Manchester, UK., Richardson A; Cerebral Function Unit, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, UK.; Division of Neuroscience, School of Biological Sciences, University of Manchester, UK., Robinson AC; Division of Neuroscience, Faculty of Biology, Medicine and Health, School of Biological Sciences, The University of Manchester, Salford Royal Hospital, Salford, M6 8HD, UK.; Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre (MAHSC), Manchester, UK., Roncaroli F; Division of Neuroscience, Faculty of Biology, Medicine and Health, School of Biological Sciences, The University of Manchester, Salford Royal Hospital, Salford, M6 8HD, UK.; Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre (MAHSC), Manchester, UK., Snowden J; Cerebral Function Unit, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, UK.; Division of Neuroscience, School of Biological Sciences, University of Manchester, UK., Allinson K; Histopathology Box 235 Cambridge University Hospital NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ., Green O; Histopathology Box 235 Cambridge University Hospital NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ., Rowe JB; Cambridge University Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, Cambridge, UK.; Medical Research Council Cognition and Brain Sciences Unit, Cambridge, UK., Singh P; Histopathology Box 235 Cambridge University Hospital NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ., Beach TG; Civin Laboratory of Neuropathology, Banner Sun Health Research Institute, Sun City, AZ 85351, USA., Serrano GE; Civin Laboratory of Neuropathology, Banner Sun Health Research Institute, Sun City, AZ 85351, USA., Flowers XE; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA., Goldman JE; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA., Heaps AC; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA., Leskinen SP; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA., Teich AF; Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA., Black SE; Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre and University of Toronto, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute., Keith JL; Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, and Laboratory Medicine and Pathobiology, University of Toronto., Masellis M; Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre and University of Toronto, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute., Bodi I; Clinical Neuropathology Department, King's College Hospital NHS Foundation Trust, London, UK.; London Neurodegenerative Diseases Brain Bank, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK., King A; Clinical Neuropathology Department, King's College Hospital NHS Foundation Trust, London, UK.; London Neurodegenerative Diseases Brain Bank, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK., Sarraj SA; Clinical Neuropathology Department, King's College Hospital NHS Foundation Trust, London, UK.; London Neurodegenerative Diseases Brain Bank, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK., Troakes C; London Neurodegenerative Diseases Brain Bank, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK., Halliday GM; University of Sydney Brain and Mind Centre and Faculty of Medicine and Health School of Medical Sciences., Hodges JR; University of Sydney Brain and Mind Centre and Faculty of Medicine and Health School of Medical Sciences., Kril JJ; University of Sydney Faculty of Medicine and Health School of Medical Sciences., Kwok JB; University of Sydney Brain and Mind Centre and Faculty of Medicine and Health School of Medical Sciences., Piguet O; University of Sydney Brain and Mind Centre and Faculty of Science School of Psychology., Gearing M; Dept. of Pathology and Laboratory Medicine, Dept. of Neurology, and Goizueta Alzheimer's Disease Center Brain Bank; Emory University School of Medicine, Atlanta, GA USA., Arzberger T; Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilians-University Munich, Germany., Roeber S; Center for Neuropathology and Prion Research, Ludwig-Maximilians-University Munich, Germany., Attems J; Newcastle Brain Tissue Resource, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK., Morris CM; Newcastle Brain Tissue Resource, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK., Thomas AJ; Newcastle Brain Tissue Resource, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK., Evers BM; University of Texas Southwestern Medical Center, Dallas, TX 75390., White CL; University of Texas Southwestern Medical Center, Dallas, TX 75390., Mechawar N; Douglas Hospital Research Centre., Sieben AA; Laboratory of Neurology, Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.; IBB-NeuroBiobank BB190113, Born Bunge Institute, Antwerp, Belgium.; Department of Pathology, Antwerp University Hospital, Antwerp, Belgium.; Department of Neurology, Ghent University Hospital, Ghent University, Belgium., Cras PP; Laboratory of Neurology, Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.; IBB-NeuroBiobank BB190113, Born Bunge Institute, Antwerp, Belgium.; Department of Neurology, Antwerp University Hospital - UZA, Antwerp, Belgium., De Vil BB; Laboratory of Neurology, Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.; IBB-NeuroBiobank BB190113, Born Bunge Institute, Antwerp, Belgium.; Department of Neurology, Antwerp University Hospital - UZA, Antwerp, Belgium., De Deyn PPPP; Laboratory of Neurochemistry and Behavior, Experimental Neurobiology Unit, University of Antwerp, Universiteitsplein 1, 2610 Antwerpen, Belgium., Duyckaerts C; Laboratoire de Neuropathologie Escourolle, Hôpital de la Salpêtrière, AP-HP, & Alzheimer Prion Team, ICM, 47 Bd de l'Hôpital, 75651 CEDEX 13 Paris, France., Le Ber I; Inserm U1127, CNRS UMR 7225, Sorbonne Université, Paris Brain Institute (ICM), Hôpital Pitié-Salpêtrière, Paris, France.; Centre de référence des démences rares ou précoces, Hôpital Pitié-Salpêtrière, Paris, France., Seihean D; Laboratoire de Neuropathologie Escourolle, Hôpital de la Salpêtrière, AP-HP, & ICM, 47 Bd de l'Hôpital, 75651 CEDEX 13 Paris, France., Turbant-Leclere S; Inserm U1127, CNRS UMR 7225, Sorbonne Université, Paris Brain Institute (ICM) Hôpital Pitié-Salpêtrière, Paris, France., MacKenzie IR; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC Canada V6T 2B5., McLean C; Department of Anatomical Pathology Alfred Heath, Melbourne, Victoria, 3004, Australia.; Victorian Brain Bank, The Florey Institute of Neuroscience of Mental Health, Parkville, Victoria, 3052, Australia., Cykowski MD; Department of Pathology and Genomic Medicine, Houston Methodist Research Institute and Weill Cornell Medicine, Houston, TX., Ervin JF; Department of Neurology, Duke University Medical Center, Durham, USA., Wang SJ; Department of Neurology, Duke University Medical Center, Durham, USA., Graff C; Division for Neurogeriatrics, Centre for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.; Unit for Hereditary Dementias, Karolinska University Hospital Solna, Stockholm, Sweden., Nennesmo I; Dept of laboratory Medicine Huddinge Karolinska Institutet, Stockholm Sweden.; Dept of Pathology, Karolinska University Hospital Solna, Stockholm, Sweden., Nagra RM; Human Brain and Spinal Fluid Resource Center, Brentwood Biomedical Research Institute, Los Angeles, CA, United States., Riehl J; UCLA - Sepulveda, Los Angeles, CA., Kovacs GG; Tanz Centre for Research in Neurodegenerative Disease (CRND) and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.; Laboratory Medicine Program and Krembil Brain Institute, University Health Network, Toronto, ON, Canada., Giaccone G; Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy., Nacmias B; Department of Neuroscience, Psychology, Drug Research and Child Health University of Florence, Florence, Italy.; IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy., Neumann M; Molecular Neuropathology of Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.; Department of Neuropathology, University Hospital of Tübingen, Tübingen, Germany., Ang LC; Department of Pathology and Laboratory Medicine, London Health Sciences Centre, London, ON, Canada.; Schulich School of Medicine and Dentistry, Western University, London. ON, Canada., Finger EC; Department of Clinical Neurological Sciences, Western University, London, ON, Canada.; Schulich School of Medicine and Dentistry, Western University, London, ON, Canada., Blauwendraat C; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA., Nalls MA; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.; Center for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, MD, USA.; Data Tecnica International LLC, Washington, DC, USA., Singleton AB; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA., Vitale D; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.; Center for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, MD, USA.; Data Tecnica International LLC, Washington, DC, USA., Cunha C; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal., Carvalho A; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal., Wszolek ZK; Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA., Morris HR; Department of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology, London, UK., Rademakers R; VIBUAntwerp Center for Molecular Neurology, University of Antwerp, Antwerp 2610, Belgium.; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA., Hardy JA; UK Dementia Research Institute at UCL, London, UK.; Reta Lila Weston Institute, University College London, Queen Square Institute of Neurology, London, UK.; Department of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, UK.; Institute for Advanced Study, The Hong Kong University of Science and Technology, Hong Kong, China., Dickson DW; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA., Rohrer JD; Dementia Research Centre, Department of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, UK., Ross OA; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.; Department of Clinical Genomics, Mayo Clinic, Jacksonville, FL 32224, USA.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2023 Apr 24. Date of Electronic Publication: 2023 Apr 24.
DOI:	10.1101/2023.04.17.23288471
Abstrakt:	Background: Pick's disease (PiD) is a rare and predominantly sporadic form of frontotemporal dementia that is classified as a primary tauopathy. PiD is pathologically defined by argyrophilic inclusion Pick bodies and ballooned neurons in the frontal and temporal brain lobes. PiD is characterised by the presence of Pick bodies which are formed from aggregated, hyperphosphorylated, 3-repeat tau proteins, encoded by the MAPT gene. The MAPT H2 haplotype has consistently been associated with a decreased disease risk of the 4-repeat tauopathies of progressive supranuclear palsy and corticobasal degeneration, however its role in susceptibility to PiD is unclear. The primary aim of this study was to evaluate the association between MAPT H2 and risk of PiD. Methods: We established the Pick's disease International Consortium (PIC) and collected 338 (60.7% male) pathologically confirmed PiD brains from 39 sites worldwide. 1,312 neurologically healthy clinical controls were recruited from Mayo Clinic Jacksonville, FL (N=881) or Rochester, MN (N=431). For the primary analysis, subjects were directly genotyped for MAPT H1-H2 haplotype-defining variant rs8070723. In secondary analysis, we genotyped and constructed the six-variant MAPT H1 subhaplotypes (rs1467967, rs242557, rs3785883, rs2471738, rs8070723, and rs7521). Findings: Our primary analysis found that the MAPT H2 haplotype was associated with increased risk of PiD (OR: 1.35, 95% CI: 1.12-1.64 P=0.002). In secondary analysis involving H1 subhaplotypes, a protective association with PiD was observed for the H1f haplotype (0.0% vs. 1.2%, P=0.049), with a similar trend noted for H1b (OR: 0.76, 95% CI: 0.58-1.00, P=0.051). The 4-repeat tauopathy risk haplotype MAPT H1c was not associated with PiD susceptibility (OR: 0.93, 95% CI: 0.70-1.25, P=0.65). Interpretation: The PIC represents the first opportunity to perform relatively large-scale studies to enhance our understanding of the pathobiology of PiD. This study demonstrates that in contrast to its protective role in 4R tauopathies, the MAPT H2 haplotype is associated with an increased risk of PiD. This finding is critical in directing isoform-related therapeutics for tauopathies. Competing Interests: M.A.N. and D.V.’s participation in this project was part of a competitive contract awarded to Data Tecnica International LLC by the National Institutes of Health to support open science research. M.A.N. also currently serves on the scientific advisory board for Character Bio Inc. and Neuron23 Inc.
Databáze:	MEDLINE
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