A head-to-head comparison of plasma biomarkers to detect Alzheimer's disease in a memory clinic

Introduction: Blood-based biomarkers for Alzheimer's disease (AD) have been widely studied, but direct comparisons of several biomarkers in clinical settings remain limited.

Methods: In this cross-sectional study, plasma biomarkers from 197 participants in the BIODEGMAR cohort (Hospital del Mar, Barcelona) were analyzed. Participants were classified based on AD cerebrospinal fluid (CSF) core biomarkers. We assessed the ability of plasma p-tau181, p-tau217, p-tau231, t-tau, and Aβ42/40 to classify Aβ pathology status.

Results: Plasma p-tau biomarkers had a greater diagnostic performance and larger effect sizes compared to t-tau and Aβ42/40 assays in detecting Aβ pathology. Among them, plasma p-tau217 consistently outperformed the others, demonstrating superior area under the curves. Furthermore, p-tau217 showed the strongest correlation between plasma and CSF levels, underscoring its potential as a reliable surrogate for CSF biomarkers.

Discussion: Several plasma biomarkers, targeting different epitopes and using different platforms, demonstrated high performance in detecting AD in a memory clinic setting.

Highlights: Plasma p-tau biomarkers demonstrated higher diagnostic performance and larger effect sizes than t-tau and Aβ42/40 assays in detecting Alzheimer's disease. Among the p-tau biomarkers, p-tau217 assays consistently outperformed the others, providing superior classification of Aβ pathology status across different phosphorylation sites. p-tau217 assays showed the strongest correlation between plasma and CSF levels, indicating its potential as a reliable surrogate for CSF biomarkers. Several plasma p-tau biomarkers can be used in a specialized memory clinic to accurately detect Alzheimer's disease.