Comparison of three plasma p-tau217 assays to detect PET-confirmed Alzheimer's pathologies.

INTRODUCTION: Plasma phosphorylated tau 217 (p-tau217) has emerged as a promising blood-based biomarker for Alzheimer's disease (AD) diagnosis, but cross-platform comparability remains unclear. We evaluated three platforms-single-molecule array (Simoa), Ella, and Lumipulse. METHODS: We measured plasma p-tau217 from 113 participants underwent amyloid and tau positron emission tomography (PET; 55 AD, 36 controls, 22 non-AD; classified by amyloid PET status). Diagnostic performance and PET correlations were assessed across all three platforms. RESULTS: All assays distinguished amyloid-positive from -negative individuals with high accuracy (89%-95%). Simoa showed superior sensitivity, Ella the smallest gray zone in a two-cutoff framework, and Lumipulse strongest tau correlation (r = 0.770). Multiple regression revealed higher amyloid β-values for Simoa/Ella (0.420-0.518) and higher tau β-values for Lumipulse (0.630). All platforms detected elevated p-tau217 in amyloid-positive individuals with substantial tau pathology despite relatively low Centiloid. DISCUSSION: All platforms accurately detect AD with platform-specific differences, which inform platform selection for clinical and research applications. TRIAL REGISTRATION: Clinical Trial Registration: UMIN Clinical Trials Registry (UMIN-CTR), Trial ID: UMIN000057548, Registration Date: April 8, 2025.