Technical and clinical validation of a novel plasma p‐tau217 assay: evaluation in real world population‐based and racially‐diverse cohorts

• DOI: 10.1002/alz.092598
• Publication Date: 2025-01-09T12:12:27Z
• Authors: Anuradha Sehrawat; Xuemei Zeng; Yijun Chen; Tara K Lafferty; Pamela C.L. Ferreira; Bruna Bellaver; Guilherme Povala; Tharick A. Pascoal; M. Ilyas Kamboh; Alexandra Gogola; Mary Ganguli; Eric E Abrahamson; Oscar L. Lopez; Victor L Villemagne; Victor L Villemagne; Milos D Ikonomovic; Beth E. Snitz; Ann D Cohen; Thomas K Karikari

Abstract Background Plasma phospho‐tau217 (p‐tau217) is a promising blood‐based biomarkers for Alzheimer's disease (AD). However, the accessibility of pTau217 tests both research and clinical applications has been constrained. Previous studies focused on highly‐phenotyped cohorts that differ substantially from wider population. To broaden access to this highly precise biomarker AD, we developed novel immunoassay p‐tau217 at University Pittsburgh (Pitt‐p‐tau217). Following thorough analytical validation, evaluated utility assay in four independent real‐world (n=503 total) reflective Methods A two‐step ultra‐sensitive was Quanterix HDX Simoa platform. Analytical validation dilution linearity, competitive binding, day‐to‐day stability, spike recovery. Clinical performed including: two population‐based, racially‐diverse medically underserved communities (the MYHAT‐Neuroimaging Human Connectome cohorts); cohort neuropathologically‐confirmed familial AD participants carrying pathogenic PSEN1 mutations. The fourth included older adults >65 years attending memory clinic. Assay performance compared with commercially‐available ALZpath‐p‐tau217 assay. Results new plasma Pitt‐p‐tau217 demonstrated high between‐run linearity dilution, substantial signal reduction when p‐tau217‐positive antigen allowed competitively bind target samples before measurement. Clinically, differentiated amyloid‐beta (Aβ) PET‐positive ‐negative cognitively unimpaired individuals areas under curve (AUCs) 0.84‐0.87, equivalent 0.87‐0.90 ALZPath correlations 0.40‐0.73. According centiloids (CL), showed stepwise higher values Aβ‐negative (CL<15) low‐burden Aβ (CL15‐25) Aβ‐positive (CL>25). By tau‐PET status, elevated tau‐PET‐positive versus negative (P<0.001) separated groups same AUC 0.71 as ALZpath‐p‐tau217. Furthermore, 5.3‐fold 3.3‐fold mutation carriers sporadic respectively controls, correlation 0.93 Conclusion Our results indicate newly‐developed assay, first an academic laboratory North America, exhibits reliable reproducible diagnostic accuracy identifying biological evidence AD. Demonstration inclusive suggests its suitability use general