Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology
Por:
Ashton N.J., Brum W.S., Di Molfetta G., Benedet A.L., Arslan B., Jonaitis E., Langhough R.E., Cody K., Wilson R., Carlsson C.M., Vanmechelen E., Montoliu-Gaya L., Lantero-Rodriguez J., Rahmouni N., Tissot C., Stevenson J., Servaes S., Therriault J., Pascoal T., Lleó A., Alcolea D., Fortea J., Rosa-Neto P., Johnson S., Jeromin A., Blennow K., Zetterberg H.
Publicada:
1 mar 2024
Ahead of Print:
1 mar 2024
Resumen:
ImportancePhosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer disease (AD) pathology, with p-tau217 considered to have the most utility. However, availability of p-tau217 tests for research and clinical use has been limited. Expanding access to this highly accurate AD biomarker is crucial for wider evaluation and implementation of AD blood tests. ObjectiveTo determine the utility of a novel and commercially available immunoassay for plasma p-tau217 to detect AD pathology and evaluate reference ranges for abnormal amyloid beta (A beta) and longitudinal change across 3 selected cohorts. Design, Setting, and ParticipantsThis cohort study examined data from 3 single-center observational cohorts: cross-sectional and longitudinal data from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort (visits October 2017-August 2021) and Wisconsin Registry for Alzheimer's Prevention (WRAP) cohort (visits February 2007-November 2020) and cross-sectional data from the Sant Pau Initiative on Neurodegeneration (SPIN) cohort (baseline visits March 2009-November 2021). Participants included individuals with and without cognitive impairment grouped by amyloid and tau (AT) status using PET or CSF biomarkers. Data were analyzed from February to June 2023. ExposuresMagnetic resonance imaging, A beta positron emission tomography (PET), tau PET, cerebrospinal fluid (CSF) biomarkers (A beta 42/40 and p-tau immunoassays), and plasma p-tau217 (ALZpath pTau217 assay). Main Outcomes and MeasuresAccuracy of plasma p-tau217 in detecting abnormal amyloid and tau pathology, longitudinal p-tau217 change according to baseline pathology status. ResultsThe study included 786 participants (mean [SD] age, 66.3 [9.7] years; 504 females [64.1%] and 282 males [35.9%]). High accuracy was observed in identifying elevated A beta (area under the curve [AUC], 0.92-0.96; 95% CI, 0.89-0.99) and tau pathology (AUC, 0.93-0.97; 95% CI, 0.84-0.99) across all cohorts. These accuracies were comparable with CSF biomarkers in determining abnormal PET signal. The detection of abnormal A beta pathology using a 3-range reference yielded reproducible results and reduced confirmatory testing by approximately 80%. Longitudinally, plasma p-tau217 values showed an annual increase only in A beta-positive individuals, with the highest increase observed in those with tau positivity. Conclusions and RelevanceThis study found that a commercially available plasma p-tau217 immunoassay accurately identified biological AD, comparable with results using CSF biomarkers, with reproducible cut-offs across cohorts. It detected longitudinal changes, including at the preclinical stage.
Filiaciones:
Ashton N.J.:
Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy, The University of Gothenburg, Mölndal, Sweden
King's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, London, United Kingdom
NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia, South London and Maudsley NHS Foundation, London, United Kingdom
Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway
Brum W.S.:
Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy, The University of Gothenburg, Mölndal, Sweden
Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
Di Molfetta G.:
Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy, The University of Gothenburg, Mölndal, Sweden
Benedet A.L.:
Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy, The University of Gothenburg, Mölndal, Sweden
Arslan B.:
Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy, The University of Gothenburg, Mölndal, Sweden
Jonaitis E.:
Wisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
Department of Medicine, Division of Geriatrics and Gerontology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
Langhough R.E.:
Wisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
Department of Medicine, Division of Geriatrics and Gerontology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
Cody K.:
Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
Wilson R.:
Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
Department of Medicine, Division of Geriatrics and Gerontology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
Carlsson C.M.:
Wisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
Department of Medicine, Division of Geriatrics and Gerontology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
Geriatric Research Education and Clinical Center, The Wm. S. Middleton Memorial Veterans Hospital, Madison, WI, United States
Vanmechelen E.:
ADx NeuroSciences, Ghent, Belgium
Montoliu-Gaya L.:
Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy, The University of Gothenburg, Mölndal, Sweden
Lantero-Rodriguez J.:
Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy, The University of Gothenburg, Mölndal, Sweden
Rahmouni N.:
Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre Intégré Universitaire de Santé et de Services Sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Canada
Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada
Tissot C.:
Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre Intégré Universitaire de Santé et de Services Sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Canada
Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada
Stevenson J.:
Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre Intégré Universitaire de Santé et de Services Sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Canada
Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada
Servaes S.:
Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre Intégré Universitaire de Santé et de Services Sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Canada
Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada
Therriault J.:
Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre Intégré Universitaire de Santé et de Services Sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Canada
Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada
Pascoal T.:
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States
Department of Neurology, University of Pittsburgh, Pittsburgh, PA, United States
Lleó A.:
Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de Sant Pau, Universitat Autònoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Catalunya, Barcelona, Spain
Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain
Alcolea D.:
Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de Sant Pau, Universitat Autònoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Catalunya, Barcelona, Spain
Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain
Fortea J.:
Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de Sant Pau, Universitat Autònoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Catalunya, Barcelona, Spain
Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain
Rosa-Neto P.:
Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre Intégré Universitaire de Santé et de Services Sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Canada
Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada
Johnson S.:
Wisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
Jeromin A.:
ALZpath, Carlsbad, CA, United States
Blennow K.:
Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy, The University of Gothenburg, Mölndal, Sweden
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Zetterberg H.:
Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy, The University of Gothenburg, Mölndal, Sweden
Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom
UK Dementia Research Institute, UCL, London, United Kingdom
Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong
hybrid, All Open Access; Hybrid Gold Open Access
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