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Plasma p-tau212 antemortem diagnostic performance and prediction of autopsy verification of Alzheimer’s disease neuropathology

Author

Listed:
  • Przemysław R. Kac

    (The Sahlgrenska Academy at the University of Gothenburg)

  • Fernando González-Ortiz

    (The Sahlgrenska Academy at the University of Gothenburg
    Sahlgrenska University Hospital)

  • Andreja Emeršič

    (University Medical Centre Ljubljana
    University of 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
    King’s College London
    Stavanger University Hospital
    SE5 8AF)

  • 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
    John 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
    Sahlgrenska University Hospital)

  • Milica Gregorič Kramberger

    (University Medical Centre Ljubljana
    University of Ljubljana
    Division of Clinical Geriatrics)

  • Jörg Hanrieder

    (The Sahlgrenska Academy at the University of Gothenburg
    Queen Square)

  • Saša Čučnik

    (University Medical Centre Ljubljana
    University of Ljubljana
    University Medical Center Ljubljana)

  • Peter Harrison

    (Bioventix Plc)

  • Henrik Zetterberg

    (The Sahlgrenska Academy at the University of Gothenburg
    Sahlgrenska University Hospital
    Queen Square
    University College London)

  • Piotr Lewczuk

    (Medical University of Białystok
    and Friedrich-Alexander Universität Erlangen-Nürnberg)

  • Madhav Thambisetty

    (National Institutes of Health)

  • Uroš Rot

    (University Medical Centre Ljubljana
    University of Ljubljana)

  • Douglas Galasko

    (University of California)

  • Kaj Blennow

    (The Sahlgrenska Academy at the University of Gothenburg
    Sahlgrenska University Hospital)

  • Thomas K. Karikari

    (The Sahlgrenska Academy at the University of Gothenburg
    University of Pittsburgh)

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.

Suggested Citation

  • Przemysław R. Kac & Fernando González-Ortiz & Andreja Emeršič & Maciej Dulewicz & Srinivas Koutarapu & Michael Turton & Yang An & Denis Smirnov & Agnieszka Kulczyńska-Przybik & Vijay R. Varma & Nichol, 2024. "Plasma p-tau212 antemortem diagnostic performance and prediction of autopsy verification of Alzheimer’s disease neuropathology," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46876-7
    DOI: 10.1038/s41467-024-46876-7
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