Analytical validation and amyloid-status discrimination of a high-throughput, research-use-only plasma p-Tau217 immunoassay
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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.
