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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Citations :  Li Y, et al. Validation of plasma amyloid-β 42/40 for detecting alzheimer disease amyloid plaques. Neurology. 2022;98:e688–e699.
Authors :  33
Identifiers
Doi : 2615
SSN : 2041-1723
Study Population
Male,Female
Mesh Terms
Humans
Other Terms
Study Design
Study Approach
Country of Study
Publication Country
England