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.
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Dulewicz M, Kac PR, Ortiz FG, Karikari TK, Kulczyńska-Przybik A, Mroczko B, Turton M, Harrison P, Maler M, Oberstein T, Kornhuber J, Hanrieder J, Zetterberg H, Blennow K, Lewczuk P
J. Neurochem. 169 (12) e70313 [2025-12-00; online 2025-12-01]
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.
PubMed 41321279
DOI 10.1111/jnc.70313
Crossref 10.1111/jnc.70313