Preanalytical stability of plasma/serum brain‐derived tau

Abstract

AbstractINTRODUCTIONWe investigated the effects of matrix type and reagent batch changes on diagnostic performances and longitudinal trajectories of brain‐derived tau (BD‐tau).METHODSWe evaluated (i) Cohort 1: paired EDTA plasma and serum from Alzheimer biomarker‐positive older adults versus controls (n = 26); and (ii) Cohort 2: n = 79 acute ischemic stroke patients with 265 longitudinal samples across four time points.RESULTSIn Cohort 1, plasma and serum BD‐tau were strongly correlated (rho = 0.96, p < 0.0001) with similar diagnostic performances (AUCs >99%) and correlations with CSF total‐tau (rho = 0.93–0.94, p < 0.0001). However, absolute concentrations were ∼40% higher in plasma versus serum. In Cohort 2, first and repeated BD‐tau measurements showed a near‐perfect correlation (rho = 0.96, p < 0.0001), with no significant between‐batch concentration differences. In longitudinal analyses, substituting ∼10% of the first‐run concentrations for the remeasured values showed overlapping estimated trajectories without significant differences at any time point.DISCUSSIONBD‐tau has equivalent diagnostic accuracies, but non‐interchangeable absolute concentrations, in plasma versus serum. Furthermore, the analytical robustness is unaffected by batch‐to‐batch reagent variations.Highlights Brain‐derived tau (BD‐tau) is a novel blood‐based biomarker that quantifies tau protein of CNS origin. Effects of preanalytical handling procedures on the quality and reproducibility of BD‐tau measures are unknown. In two cohorts of n = 105 participants, we compared BD‐tau concentrations and diagnostic performances in paired plasma and serum samples, and evaluated impacts of batch‐to‐batch reagent variations. Paired plasma and serum showed equivalent diagnostic performances to separate amyloid‐positive AD from amyloid‐negative controls, indicating both can be used independently. Repeated measurements and longitudinal trajectories of plasma BD‐tau were unaffected by batch‐to‐batch reagent variation.