Plasma p-tau212 antemortem diagnostic performance and prediction of autopsy verification of Alzheimer's disease neuropathology.
Journal: Nature communications
Volume: 15
Issue: 1
Year of Publication: 2024
Affiliated Institutions:
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, , Sweden. przemyslaw.kac@gu.se.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, , Sweden.
Department of Neurology, University Medical Centre Ljubljana, Ljubljana, , Slovenia.
Bioventix Plc, Farnham, GU SX, UK.
Brain Aging and Behavior Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, , USA.
Department of Neurosciences, University of California, San Diego, CA, , USA.
Department of Neurodegeneration Diagnostics, Medical University of Białystok, Białystok, -, Poland.
Clinical and Translational Neuroscience Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, , USA.
Dementia Disorders Center, Medical University of Wrocław, -, Ścinawa, Poland.
Department of Neurology, Medical University of Wrocław, -, Wrocław, Poland.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, , USA.
Department of Neurodegenerative diseases, UCL Queen Square Institute of Neurology, WCN PJ, London, UK.
Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, , USA.
Abstract summary
Blood phosphorylated tau (p-tau) biomarkers, including p-tau217, show high associations with Alzheimer's disease (AD) neuropathologic change and clinical stage. Certain plasma p-tau217 assays recognize tau forms phosphorylated additionally at threonine-212, but the contribution of p-tau212 alone to AD is unknown. We developed a blood-based immunoassay that is specific to p-tau212 without cross-reactivity to p-tau217. Here, we examined the diagnostic utility of plasma p-tau212. In five cohorts (n = 388 participants), plasma p-tau212 showed high performances for AD diagnosis and for the detection of both amyloid and tau pathology, including at autopsy as well as in memory clinic populations. The diagnostic accuracy and fold changes of plasma p-tau212 were similar to those for p-tau217 but higher than p-tau181 and p-tau231. Immunofluorescent staining of brain tissue slices showed prominent p-tau212 reactivity in neurofibrillary tangles that co-localized with p-tau217 and p-tau202/205. These findings support plasma p-tau212 as a peripherally accessible biomarker of AD pathophysiology.
Authors & Co-authors:
Kac
González-Ortiz
Emeršič
Dulewicz
Koutarapu
Turton
An
Smirnov
Kulczyńska-Przybik
Varma
Ashton
Montoliu-Gaya
Camporesi
Winkel
Paradowski
Moghekar
Troncoso
Lashley
Brinkmalm
Resnick
Mroczko
Kvartsberg
Gregorič Kramberger
Hanrieder
Čučnik
Harrison
Zetterberg
Lewczuk
Thambisetty
Rot
Galasko
Blennow
Karikari
Study Outcome
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