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

Journal article

P. Kac, Fernando González-Ortiz, A. Emeršič, M. Dulewicz, Srinivas Koutarapu, Michael Turton, Yang An, Denis S Smirnov, A. Kulczyńska-Przybik, Vijay R Varma, N. Ashton, L. Montoliu‐Gaya, Elena Camporesi, Izabela Winkel, Bogusław Paradowski, A. Moghekar, Juan C. Troncoso, T. Lashley, G. Brinkmalm, Susan M. Resnick, B. Mroczko, Hlin Kvartsberg, M. Gregoric Kramberger, Jörg Hanrieder, S. Čučnik, Peter Harrison, H. Zetterberg, P. Lewczuk, M. Thambisetty, U. Rot, Douglas Galasko, K. Blennow, T. Karikari
Nature Communications, 2024

Semantic Scholar DOI PubMedCentral PubMed

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APA Click to copy
Kac, P., González-Ortiz, F., Emeršič, A., Dulewicz, M., Koutarapu, S., Turton, M., … Karikari, T. (2024). Plasma p-tau212 antemortem diagnostic performance and prediction of autopsy verification of Alzheimer’s disease neuropathology. Nature Communications.

Chicago/Turabian Click to copy
Kac, P., Fernando González-Ortiz, A. Emeršič, M. Dulewicz, Srinivas Koutarapu, Michael Turton, Yang An, et al. “Plasma p-tau212 Antemortem Diagnostic Performance and Prediction of Autopsy Verification of Alzheimer’s Disease Neuropathology.” Nature Communications (2024).

MLA Click to copy
Kac, P., et al. “Plasma p-tau212 Antemortem Diagnostic Performance and Prediction of Autopsy Verification of Alzheimer’s Disease Neuropathology.” Nature Communications, 2024.

BibTeX Click to copy

@article{p2024a,
  title = {Plasma p-tau212 antemortem diagnostic performance and prediction of autopsy verification of Alzheimer’s disease neuropathology},
  year = {2024},
  journal = {Nature Communications},
  author = {Kac, P. and González-Ortiz, Fernando and Emeršič, A. and Dulewicz, M. and Koutarapu, Srinivas and Turton, Michael and An, Yang and Smirnov, Denis S and Kulczyńska-Przybik, A. and Varma, Vijay R and Ashton, N. and Montoliu‐Gaya, L. and Camporesi, Elena and Winkel, Izabela and Paradowski, Bogusław and Moghekar, A. and Troncoso, Juan C. and Lashley, T. and Brinkmalm, G. and Resnick, Susan M. and Mroczko, B. and Kvartsberg, Hlin and Kramberger, M. Gregoric and Hanrieder, Jörg and Čučnik, S. and Harrison, Peter and Zetterberg, H. and Lewczuk, P. and Thambisetty, M. and Rot, U. and Galasko, Douglas and Blennow, K. and Karikari, T.}
}

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. A range of blood-based biomarkers have shown high specificity for Alzheimer’s disease (AD) pathophysiology with phosphorylated-tau (p-tau) being the most promising test. Here, the authors show the utility of plasma p-tau212 in autopsy-confirmed AD and memory clinic patient cohorts.