Analytical validation and amyloid-status discrimination of a high-throughput, research-use-only plasma p-Tau217 immunoassay
Year: 2026
Type: preprint
Abstract: Background Plasma phosphorylated tau at threonine 217 (p-Tau217) is a leading blood-based biomarker for Alzheimer’s disease (AD). Robust analytical characterization on high-throughput platforms is essential for research use and clinical translation. Objective To evaluate the analytical performance of an automated plasma p-Tau217 immunoassay and characterize its discrimination of PET-defined amyloid status. Methods We performed analytical validation of the Access Research Use Only (RUO) plasma p-Tau217 immunoassay on the Beckman Coulter DxI 9000 Access Immunoassay Analyzer and evaluated biomarker discrimination of PET-defined amyloid pathology in a subset of the Bio-Hermes-001 cohort spanning the symptomatic cognitive continuum (mild cognitive impairment or mild AD dementia; cognitively unimpaired participants excluded; n = 449). Analytical precision, sensitivity, linearity, specificity, interference, and sample stability were assessed per Clinical and Laboratory Standards Institute guidelines. Discrimination of PET-defined amyloid status was evaluated using receiver operating characteristic curve and indeterminate zone analyses. Results The assay demonstrated high precision (within-laboratory CV ≤7.1%), excellent sensitivity (limit of detection 0.018–0.021 pg/mL), linearity across the analytical measuring range (R² > 0.99), strong epitope specificity (≤1.0% cross-reactivity with other tau phosphoisoforms), and minimal interference from over 60 endogenous and exogenous substances. In 449 research participants plasma p-Tau217 showed strong discrimination between amyloid-positive and amyloid-negative groups (AUC 0.881; 95% CI 0.846–0.915). Application of indeterminate zones systematically improved classification metrics at the cost of fewer definitive classifications. Conclusions These findings support the Access p-Tau217 (RUO) assay as a robust, high-throughput assay for plasma biomarker-based discrimination of PET-defined amyloid pathology in AD applications.
Source: medRxiv
Institutions: Danaher (United States), University of Wisconsin–Madison, Sahlgrenska University Hospital, National Hospital for Neurology and Neurosurgery, UCL Queen Square Institute of Neurology, University of Gothenburg, UK Dementia Research Institute, University College London, Johns Hopkins University
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7206192983