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 and Thomas K. Karikari
Additional contact information
Przemysław R. Kac: The Sahlgrenska Academy at the University of Gothenburg
Fernando González-Ortiz: The Sahlgrenska Academy at the University of Gothenburg
Andreja Emeršič: University Medical Centre Ljubljana
Maciej Dulewicz: The Sahlgrenska Academy at the University of Gothenburg
Srinivas Koutarapu: The Sahlgrenska Academy at the University of Gothenburg
Michael Turton: Bioventix Plc
Yang An: National Institutes of Health
Denis Smirnov: University of California
Agnieszka Kulczyńska-Przybik: Medical University of Białystok
Vijay R. Varma: National Institutes of Health
Nicholas J. Ashton: The Sahlgrenska Academy at the University of Gothenburg
Laia Montoliu-Gaya: The Sahlgrenska Academy at the University of Gothenburg
Elena Camporesi: The Sahlgrenska Academy at the University of Gothenburg
Izabela Winkel: Medical University of Wrocław
Bogusław Paradowski: Medical University of Wrocław
Abhay Moghekar: Johns Hopkins University School of Medicine
Juan C. Troncoso: Johns Hopkins University School of Medicine
Tammaryn Lashley: UCL Queen Square Institute of Neurology
Gunnar Brinkmalm: The Sahlgrenska Academy at the University of Gothenburg
Susan M. Resnick: National Institutes of Health
Barbara Mroczko: Medical University of Białystok
Hlin Kvartsberg: The Sahlgrenska Academy at the University of Gothenburg
Milica Gregorič Kramberger: University Medical Centre Ljubljana
Jörg Hanrieder: The Sahlgrenska Academy at the University of Gothenburg
Saša Čučnik: University Medical Centre Ljubljana
Peter Harrison: Bioventix Plc
Henrik Zetterberg: The Sahlgrenska Academy at the University of Gothenburg
Piotr Lewczuk: Medical University of Białystok
Madhav Thambisetty: National Institutes of Health
Uroš Rot: University Medical Centre Ljubljana
Douglas Galasko: University of California
Kaj Blennow: The Sahlgrenska Academy at the University of Gothenburg
Thomas K. Karikari: The Sahlgrenska Academy at the University of Gothenburg

Nature Communications, 2024, vol. 15, issue 1, 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.

Date: 2024
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DOI: 10.1038/s41467-024-46876-7

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