Multi‐platform comparison of plasma phosphorylated tau assays: analytical and workflow factors drive clinical implementation decisions
Olga Sandoval‐Boczkowska, John R. Best, Rachael J. Y. Smith, Laura Burns, Cyril Helbling, Ging‐Yuek Robin Hsiung, Jacqueline A. Pettersen, Philip E. Lee, Alexandre Henri‐Bhargava, Haakon B. Nygaard, Mari L. DeMarcoAbstract
INTRODUCTION
Multiple plasma phosphorylated tau assays are now commercially available for Alzheimer's disease (AD), yet clinical laboratories lack comprehensive comparative data to guide implementation.
METHODS
We assessed diagnostic accuracy and analytical performance in 273 participants with paired plasma and cerebrospinal fluid (CSF). CSF AD core biomarkers served as the reference standard. Index tests included three plasma tau phosphorylated at residue 217 (pTau217) assays (Roche, Fujirebio, Meso Scale Discovery [MSD]) and a pTau181 assay (Roche).
RESULTS
Participants: median age 70 [IQR: 64 to 76] years, 42% female, and 60% AD‐positive. pTau217 assays showed comparable accuracy (area under the curve [AUC] 0.88 to 0.89) exceeding pTau181 (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 (two cycles).
DISCUSSION
With comparable diagnostic accuracy across pTau217 platforms, analytical performance, and operational suitability became decisive implementation differentiators.