Clinical Validation of Novel Immunoassays for Plasma Phosphorylated Tau 217, 212, 181, 231, and Brain-Derived Tau Across the Biochemical Spectrum of Alzheimer's Disease

Dulewicz M, Kac PR, Ortiz FG, Karikari TK, Kulczyńska-Przybik A, Mroczko B, Turton M, Harrison P, Maler JM, Oberstein T, Kornhuber J, Hanrieder J, Zetterberg H, Blennow K, Lewczuk P (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Journal of neurochemistry

Book Volume: 169

Article Number: e70313

Journal Issue: 12

DOI: 10.1111/jnc.70313

Abstract

Plasma biomarkers have emerged as promising less invasive alternatives for Alzheimer's disease (AD) detection. However, the diagnostic performance of phosphorylated tau (p-tau) isoforms remains incompletely validated. In a cohort of 160 patients from a memory clinic, plasma levels of p-tau217, p-tau212, p-tau181, p-tau231, and BD-tau were measured using Single Molecule Array (Simoa) in-house assays, alongside NFL and GFAP. Subjects were classified using the Erlangen Score into Controls (n = 53), neurochemically possible AD (n = 27), and probable AD (n = 80). Plasma concentrations of all p-tau isoforms were significantly elevated in both Possible AD and Probable AD groups compared to Controls (p < 0.001). Notably, p-tau217 exhibited the highest diagnostic accuracy (AUC = 0.954) and correlated with CSF classical biomarkers. A positive result for p-tau217 increases the probability of AD almost fivefold. Plasma p-tau217 reflects AD neurochemical changes and has high negative predictive value, supporting its use as a screening tool. However, moderate PPV suggests the need for confirmatory testing to ensure an accurate diagnosis. (Figure presented.).

Authors with CRIS profile

Juan Manuel Maler Department of Psychiatry and Psychotherapy Timo Oberstein Department of Psychiatry and Psychotherapy Johannes Kornhuber Lehrstuhl für Psychiatrie und Psychotherapie

Involved external institutions

Sahlgrenska University Hospital / Sahlgrenska Universitetssjukhuset SE Sweden (SE) Medical University of Bialystok PL Poland (PL) Bioventix GB United Kingdom (GB)

How to cite

APA:

Dulewicz, M., Kac, P.R., Ortiz, F.G., Karikari, T.K., Kulczyńska-Przybik, A., Mroczko, B.,... Lewczuk, P. (2025). Clinical Validation of Novel Immunoassays for Plasma Phosphorylated Tau 217, 212, 181, 231, and Brain-Derived Tau Across the Biochemical Spectrum of Alzheimer's Disease. Journal of neurochemistry, 169(12). https://doi.org/10.1111/jnc.70313

MLA:

Dulewicz, Maciej, et al. "Clinical Validation of Novel Immunoassays for Plasma Phosphorylated Tau 217, 212, 181, 231, and Brain-Derived Tau Across the Biochemical Spectrum of Alzheimer's Disease." Journal of neurochemistry 169.12 (2025).

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