Plasma pTau181 and pTau217 predict asymptomatic amyloid accumulation equally well as amyloid PET.

Autor:	De Meyer S; Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven, 3000 Leuven, Belgium.; Laboratory for Molecular Neurobiomarker Research, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven, 3000 Leuven, Belgium., Schaeverbeke JM; Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven, 3000 Leuven, Belgium., Luckett ES; Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven, 3000 Leuven, Belgium.; Laboratory for Complex Genetics, Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium., Reinartz M; Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven, 3000 Leuven, Belgium., Blujdea ER; Neurochemistry Laboratory, Department of Clinical Chemistry, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, 1081 HV Amsterdam, The Netherlands., Cleynen I; Laboratory for Complex Genetics, Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium., Dupont P; Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven, 3000 Leuven, Belgium., Van Laere K; Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, 3000 Leuven, Belgium.; Division of Nuclear Medicine, UZ Leuven, 3000 Leuven, Belgium., Vanbrabant J; ADx NeuroSciences NV, 9052 Ghent, Belgium., Stoops E; ADx NeuroSciences NV, 9052 Ghent, Belgium., Vanmechelen E; ADx NeuroSciences NV, 9052 Ghent, Belgium., di Molfetta G; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, S-431 80 Mölndal, Sweden., Zetterberg H; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, S-431 80 Mölndal, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, S-431 80 Mölndal, Sweden.; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, WC1N 3BG London, UK.; UK Dementia Research Institute at UCL, WC1N 3BG London, UK.; Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA., Ashton NJ; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, S-431 80 Mölndal, Sweden., Teunissen CE; Neurochemistry Laboratory, Department of Clinical Chemistry, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, 1081 HV Amsterdam, The Netherlands., Poesen K; Laboratory for Molecular Neurobiomarker Research, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven, 3000 Leuven, Belgium.; Laboratory Medicine Department, UZ Leuven, 3000 Leuven, Belgium., Vandenberghe R; Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven, 3000 Leuven, Belgium.; Neurology Department, UZ Leuven, 3000 Leuven, Belgium.
Jazyk:	angličtina
Zdroj:	Brain communications [Brain Commun] 2024 May 23; Vol. 6 (4), pp. fcae162. Date of Electronic Publication: 2024 May 23 (Print Publication: 2024).
DOI:	10.1093/braincomms/fcae162
Abstrakt:	The dynamic phase of preclinical Alzheimer's disease, as characterized by accumulating cortical amyloid-β, is a window of opportunity for amyloid-β-lowering therapies to have greater efficacy. Biomarkers that accurately predict amyloid-β accumulation may be of critical importance for participant inclusion in secondary prevention trials and thus enhance development of early Alzheimer's disease therapies. We compared the abilities of baseline plasma pTau181, pTau217 and amyloid-β PET load to predict future amyloid-β accumulation in asymptomatic elderly. In this longitudinal cohort study, baseline plasma pTau181 and pTau217 were quantified using single molecule array assays in cognitively unimpaired elderly selected from the community-recruited F-PACK cohort based on the availability of baseline plasma samples and longitudinal amyloid-β PET data (median time interval = 5 years, range 2-10 years). The predictive abilities of pTau181, pTau217 and PET-based amyloid-β measures for PET-based amyloid-β accumulation were investigated using receiver operating characteristic analyses, correlations and stepwise regression analyses. We included 75 F-PACK subjects (mean age = 70 years, 48% female), of which 16 were classified as amyloid-β accumulators [median (interquartile range) Centiloid rate of change = 3.42 (1.60) Centiloids/year). Plasma pTau181 [area under the curve (95% confidence interval) = 0.72 (0.59-0.86)] distinguished amyloid-β accumulators from non-accumulators with similar accuracy as pTau217 [area under the curve (95% confidence interval) = 0.75 (0.62-0.88) and amyloid-β PET [area under the curve (95% confidence interval) = 0.72 (0.56-0.87)]. Plasma pTau181 and pTau217 strongly correlated with each other ( r = 0.93, P false discovery rate < 0.001) and, together with amyloid-β PET, similarly correlated with amyloid-β rate of change ( r pTau181 = 0.33, r pTau217 = 0.36, r amyloid-β PET = 0.35, all P false discovery rate ≤ 0.01). Addition of plasma pTau181, plasma pTau217 or amyloid-β PET to a linear demographic model including age, sex and APOE-ε4 carriership similarly improved the prediction of amyloid-β accumulation (ΔAkaike information criterion ≤ 4.1). In a multimodal biomarker model including all three biomarkers, each biomarker lost their individual predictive ability. These findings indicate that plasma pTau181, plasma pTau217 and amyloid-β PET convey overlapping information and therefore predict the dynamic phase of asymptomatic amyloid-β accumulation with comparable performances. In clinical trial recruitment, confirmatory PET scans following blood-based prescreening might thus not provide additional value for detecting participants in these early disease stages who are destined to accumulate cortical amyloid-β. Given the moderate performances, future studies should investigate whether integrating plasma pTau species with other factors can improve performance and thus enhance clinical and research utility. Competing Interests: S.D.M., J.M.S., E.S.L., M.R., E.R.B., I.C., P.D., G.d.M. and K.P. report no disclosures. J.V. and E.S. are full-time paid employees, and EV is co-founder of ADx Neurosciences. K.V.L. has performed contract research through UZ/KU Leuven as principal investigator for GE Healthcare and received speaker fees from GE Healthcare. 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, Novo Nordisk 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). N.J.A. has given lectures in symposia sponsored by Eli Lilly, Roche Diagnostics and Quanterix. N.J.A. has declined paid opportunities from ALZpath. C.E.T. performed contract research for Acumen, ADx Neurosciences, AC-Immune, Alamar, Aribio, Axon Neurosciences, Beckman Coulter, BioConnect, Bioorchestra, Brainstorm Therapeutics, Celgene, Cognition Therapeutics, EIP Pharma, Eisai, Eli Lilly, Fujirebio, Grifols, Instant Nano Biosensors, Merck, Novo Nordisk, Olink, PeopleBio, Quanterix, Roche, Toyama and Vivoryon. She serves on editorial boards of Medidact Neurologie/Springer, Alzheimer’s Research and Therapy and Neurology: Neuroimmunology & Neuroinflammation. R.V.’s institution has had a clinical trial agreement for Phase 1 and 2 studies with GE Healthcare, which provided [18F]flutemetamol for this study. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)
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