Multi-Platform Comparison of Plasma Phosphorylated Tau Assays: Analytical and Workflow Factors Drive Clinical Implementation Decisions

Multiple plasma phosphorylated tau assays are now commercially available for detection of Alzheimers disease (AD) pathology, yet clinical laboratories lack a comprehensive comparative evaluation to guide implementation decisions. Diagnostic accuracy and analytical performance were assessed in a cohort of 273 participants with paired EDTA plasma and CSF specimens. CSF AD core biomarkers were used as the reference standard, and index tests included three plasma pTau217 assays by Roche, Fujirebio, and Meso Scale Discovery [MSD], and a pTau181 assay by Roche. Participants had a median age of 70 [IQR: 64-76] years, 42% were female and 60% were AD-positive. Diagnostic performance was statistically similar across all pTau217 assays (range: 0.88-0.89 area under the receiver operating characteristic curve [AUC]) with the pTau181 assay having lower accuracy (AUC = 0.85). All assays were resistant to hemolysis, icterus, and lipemia. Automated assays (Roche, Fujirebio) showed superior analytical precision and freeze/thaw stability ([≥]6 cycles) compared to the manual MSD assay (2 cycles). Given that plasma pTau217 assays demonstrated high and comparable accuracy in this head-to-head comparison, their differences in analytical performance characteristics and general clinical laboratory suitability became the differentiating factors for clinical implementation.