Nature Communications (Mar 2024)
Plasma p-tau212 antemortem diagnostic performance and prediction of autopsy verification of Alzheimer’s disease neuropathology
- Przemysław R. Kac,
- Fernando González-Ortiz,
- Andreja Emeršič,
- Maciej Dulewicz,
- Srinivas Koutarapu,
- Michael Turton,
- Yang An,
- Denis Smirnov,
- Agnieszka Kulczyńska-Przybik,
- Vijay R. Varma,
- Nicholas J. Ashton,
- Laia Montoliu-Gaya,
- Elena Camporesi,
- Izabela Winkel,
- Bogusław Paradowski,
- Abhay Moghekar,
- Juan C. Troncoso,
- Tammaryn Lashley,
- Gunnar Brinkmalm,
- Susan M. Resnick,
- Barbara Mroczko,
- Hlin Kvartsberg,
- Milica Gregorič Kramberger,
- Jörg Hanrieder,
- Saša Čučnik,
- Peter Harrison,
- Henrik Zetterberg,
- Piotr Lewczuk,
- Madhav Thambisetty,
- Uroš Rot,
- Douglas Galasko,
- Kaj Blennow,
- Thomas K. Karikari
Affiliations
- Przemysław R. Kac
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg
- Fernando González-Ortiz
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg
- Andreja Emeršič
- Department of Neurology, University Medical Centre Ljubljana
- Maciej Dulewicz
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg
- Srinivas Koutarapu
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg
- Michael Turton
- Bioventix Plc
- Yang An
- Brain Aging and Behavior Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health
- Denis Smirnov
- Department of Neurosciences, University of California
- Agnieszka Kulczyńska-Przybik
- Department of Neurodegeneration Diagnostics, Medical University of Białystok
- Vijay R. Varma
- Clinical and Translational Neuroscience Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health
- Nicholas J. Ashton
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg
- Laia Montoliu-Gaya
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg
- Elena Camporesi
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg
- Izabela Winkel
- Dementia Disorders Center, Medical University of Wrocław
- Bogusław Paradowski
- Department of Neurology, Medical University of Wrocław
- Abhay Moghekar
- Department of Neurology, Johns Hopkins University School of Medicine
- Juan C. Troncoso
- Department of Neurology, Johns Hopkins University School of Medicine
- Tammaryn Lashley
- Department of Neurodegenerative diseases, UCL Queen Square Institute of Neurology
- Gunnar Brinkmalm
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg
- Susan M. Resnick
- Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health
- Barbara Mroczko
- Department of Neurodegeneration Diagnostics, Medical University of Białystok
- Hlin Kvartsberg
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg
- Milica Gregorič Kramberger
- Department of Neurology, University Medical Centre Ljubljana
- Jörg Hanrieder
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg
- Saša Čučnik
- Department of Neurology, University Medical Centre Ljubljana
- Peter Harrison
- Bioventix Plc
- Henrik Zetterberg
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg
- Piotr Lewczuk
- Department of Neurodegeneration Diagnostics, Medical University of Białystok
- Madhav Thambisetty
- Clinical and Translational Neuroscience Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health
- Uroš Rot
- Department of Neurology, University Medical Centre Ljubljana
- Douglas Galasko
- Department of Neurosciences, University of California
- Kaj Blennow
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg
- Thomas K. Karikari
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg
- DOI
- https://doi.org/10.1038/s41467-024-46876-7
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 16
Abstract
Abstract 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.
