The Alzheimer's Association Global Biomarker Standardization Consortium (GBSC) plasma phospho-tau Round Robin study.

Autor:	Ashton NJ; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.; King's College London, Institute of Psychiatry, Psychology and Neuroscience Maurice Wohl Institute Clinical Neuroscience Institute London, UK.; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation London, UK.; Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway., Keshavan A; Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, UK., Brum WS; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.; Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil., Andreasson U; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden., Arslan B; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden., Droescher M; AbbVie Deutschland GmbH & Co. KG, Neuroscience Research, Knollstrasse, 67061 Ludwigshafen, Germany., Barghorn S; AbbVie Deutschland GmbH & Co. KG, Neuroscience Research, Knollstrasse, 67061 Ludwigshafen, Germany., Vanbrabant J; ADx NeuroSciences N.V., Technologiepark 6, 9052 Ghent, Belgium., Lambrechts C; ADx NeuroSciences N.V., Technologiepark 6, 9052 Ghent, Belgium., Van Loo M; ADx NeuroSciences N.V., Technologiepark 6, 9052 Ghent, Belgium., Stoops E; ADx NeuroSciences N.V., Technologiepark 6, 9052 Ghent, Belgium., Iyengar S; Alamar Biosciences, Inc., Fremont, CA, USA., Ji H; Alamar Biosciences, Inc., Fremont, CA, USA., Xu X; Alamar Biosciences, Inc., Fremont, CA, USA., Forrest-Hay A; Alamar Biosciences, Inc., Fremont, CA, USA., Zhang B; Alamar Biosciences, Inc., Fremont, CA, USA., Luo Y; Alamar Biosciences, Inc., Fremont, CA, USA., Jeromin A; ALZpath Inc., Carlsbad, CA, USA., Vandijck M; Fujirebio Europe N.V., Ghent, Belgium., Bastard NL; Fujirebio Europe N.V., Ghent, Belgium., Kolb H; Enigma Biomedical Group, CA, USA., Triana-Baltzer G; Neuroscience Biomarkers, Janssen Research and Development, La Jolla, California, USA., Bali D; Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund 22184, Sweden., Janelidze S; Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund 22184, Sweden., Yang SY; MagQu Co., Ltd., New Taipei City 112, Taiwan., Demos C; Meso Scale Diagnostics, LLC., Rockville, Maryland, USA., Romero D; Meso Scale Diagnostics, LLC., Rockville, Maryland, USA., Sigal G; Meso Scale Diagnostics, LLC., Rockville, Maryland, USA., Wohlstadter J; Meso Scale Diagnostics, LLC., Rockville, Maryland, USA., Malyavantham K; Quanterix Corp, Billerica, MA, USA., Khare M; Quanterix Corp, Billerica, MA, USA., Jethwa A; Roche Diagnostics GmbH, Penzberg, Germany., Stoeckl L; Roche Diagnostics GmbH, Penzberg, Germany., Gobom J; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden., Kac PR; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden., Gonzalez-Ortiz F; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden., Montoliu-Gaya L; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden., Hansson O; Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund 22184, Sweden.; Memory Clinic, Skåne University Hospital, Malmö 20502, Sweden., Rissman RA; Alzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, CA 92121, USA., Carillo MC; Division of Medical & Scientific Relations, Alzheimer's Association, Chicago, Illinois, USA., Shaw LM; Department of pathology & laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104., Blennow K; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.; Memory Clinic, Skåne University Hospital, Malmö 20502, Sweden.; Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.; Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, P.R. China., Schott JM; Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, UK.; UK Dementia Research Institute, University College London, London, UK., Zetterberg H; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.; Memory Clinic, Skåne University Hospital, Malmö 20502, Sweden.; UK Dementia Research Institute, University College London, London, UK.; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.; Hong Kong Center for Neurodegenerative Diseases, Science Park, Hong Kong, China.; School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2024 Aug 22. Date of Electronic Publication: 2024 Aug 22.
DOI:	10.1101/2024.08.22.24312244
Abstrakt:	Background: Phosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer's disease (AD) pathology. Multiple p-tau biomarkers on several analytical platforms are poised for clinical use. The Alzheimer's Association Global Biomarker Standardisation Consortium plasma phospho-tau Round Robin study engaged assay developers in a blinded case-control study on plasma p-tau, aiming to learn which assays provide the largest fold-changes in AD compared to non-AD, have the strongest relationship between plasma and cerebrospinal fluid (CSF), and show the most consistent relationships between methods (commutability) in measuring both patient samples and candidate reference materials (CRM). Methods: Thirty-three different p-tau biomarker assays, built on eight different analytical platforms, were used to quantify paired plasma and CSF samples from 40 participants. AD biomarker status was categorised as "AD pathology" (n=25) and "non-AD pathology" (n=15) by CSF Aβ42/Aβ40 (US-FDA; CE-IVDR) and p-tau181 (CE-IVDR) methods. The commutability of four CRM, at three concentrations, was assessed across assays. Findings: Plasma p-tau217 consistently demonstrated higher fold-changes between AD and non-AD pathology groups, compared to other p-tau epitopes. Fujirebio LUMIPULSE G, UGOT IPMS, and Lilly MSD p-tau217 assays provided the highest median fold-changes. In CSF, p-tau217 assays also performed best, and exhibited substantially larger fold-changes than their plasma counterparts, despite similar diagnostic performance. P-tau217 showed the strongest correlations between plasma assays (rho=0.81 to 0.97). Plasma p-tau levels were weakly-to-moderately correlated with CSF p-tau, and correlations were non-significant within the AD group alone. The evaluated CRM were not commutable across assays. Interpretation: Plasma p-tau217 measures had larger fold-changes and discriminative accuracies for detecting AD pathology, and better agreement across platforms than other plasma p-tau variants. Plasma and CSF markers of p-tau, measured by immunoassays, are not substantially correlated, questioning the interchangeability of their continuous relationship. Further work is warranted to understand the pathophysiology underlying this dissociation, and to develop suitable reference materials facilitating cross-assay standardisation. Funding: Alzheimer's Association (#ADSF-24-1284328-C). Competing Interests: CONFLICTS OF INTEREST All biomarker measurements were performed by the assay developers in-house without cost. ALZpath p-tau217 was performed at the University of Gothenburg (UGOT) and Lilly immunoassays were performed at the University of Lund. C2N Diagnostics declined to participate in the study. N.J.A. has given lectures in symposia sponsored by Eli-Lilly, Roche Diagnostics, and Quanterix. NJA has declined paid opportunities from ALZpath. A.K. has no conflicts of interest. W.S.B. has no conflicts of interest. L.G. has no conflicts of interest. U.A. has no conflicts of interest. B.A. has no conflicts of interest. M.D. is an employee of AbbVie and holds stock or stock options. S.B. is an employee of AbbVie and holds stock or stock options. J.V. is employee of ADx NeuroSciences. C.L. is an employee of ADx NeuroSciences. M.V.L. is an employee of ADx NeuroSciences. E.S. is an employee of ADx NeuroSciences. S.I. is an employee of Alamar Biosciences H.Y.J. is an employee of Alamar Biosciences X.Y. is an employee of Alamar Biosciences A.F-H. is an employee of Alamar Biosciences B.Z. is an employee of Alamar Biosciences Y.L. is an employee of Alamar Biosciences A.Jeromin is an employee of ALZpath, Inc., and has stock options. M.V. is an employee of Fujirebio Europe N.V. N.L.B. is an employee of Fujirebio Europe N.V H.K. is a former employee of Janssen R&D D.B. has no conflicts of interest. G.T-B. is an employee of Janssen R&D and has stock options. D.B. has no conflicts of interest. S.J. has no conflicts of interest. S-Y.Y is an employee of MagQu Co., Ltd.C.D. C.D. is employee of Meso Scale Diagnostics, LLC D.R. is an employee of Meso Scale Diagnostics, LLC G.S. is an employee of Meso Scale Diagnostics, LLC J.W. is an employee of Meso Scale Diagnostics, LLC K.M. is an employee of Quanterix M.K. is an employee of Quanterix A.Jethwa is a full-time employee of Roche Diagnostics GmbH, Penzberg, Germany. L.S. is a full-time employee of Roche Diagnostics GmbH, Penzberg, Germany. O.H. has acquired research support (for the institution) from AVID Radiopharmaceuticals, Biogen, C2N Diagnostics, Eli Lilly, Eisai, Fujirebio, GE Healthcare, and Roche. In the past 2 years, he has received consultancy/speaker fees from AC Immune, Alzpath, BioArctic, Biogen, Bristol Meyer Squibb, Cerveau, Eisai, Eli Lilly, Fujirebio, Merck, Novartis, Novo Nordisk, Roche, Sanofi and Siemens. R.R has no conflicts of interest. J.G. has no conflicts of interest. P.K. has no conflicts of interest. F.G-O. has no conflicts of interest. L.M-G. has no conflicts of interest. L.M.S. has served as a consultant or on advisory boards for Biogen, Roche Diagnostics, Fujirebio; receives grant support from NIA/ADNI with QC oversight responsibilities and in-kind support from Fujirebio and Roche Diagnostics automated immunoassay platforms and reagents. K.B. has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, BioArctic, Biogen, JOMDD/Shimadzu, Julius Clinical, Lilly, MagQu, Novartis, Ono Pharma, Pharmatrophix, Prothena, Roche Diagnostics, and Siemens Healthineers, and is a cofounder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. J.M.S. has received research funding from Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly); consulted for Roche Pharmaceuticals, Biogen, Merck, and Eli Lilly; given educational lectures sponsored by GE Healthcare, Eli Lilly, and Biogen; and is Chief Medical Officer for ARUK. H.Z. has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work).
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu