Longitudinal plasma phosphorylated‐tau217 and other related biomarkers in a non‐demented Alzheimer's risk‐enhanced sample

Abstract

AbstractINTRODUCTIONUnderstanding longitudinal change in key plasma biomarkers will aid in detecting presymptomatic Alzheimer's disease (AD).METHODSSerial plasma samples from 424 Wisconsin Registry for Alzheimer's Prevention participants were analyzed for phosphorylated‐tau217 (p‐tau217; ALZpath) and other AD biomarkers, to study longitudinal trajectories in relation to disease, health factors, and cognitive decline. Of the participants, 18.6% with known amyloid status were amyloid positive (A+); 97.2% were cognitively unimpaired (CU).RESULTSIn the CU, amyloid‐negative (A–) subset, plasma p‐tau217 levels increased modestly with age but were unaffected by body mass index and kidney function. In the whole sample, average p‐tau217 change rates were higher in those who were A+ (e.g., simple slopes(se) for A+ and A– at age 60 were 0.232(0.028) and 0.038(0.013))). High baseline p‐tau217 levels predicted faster preclinical cognitive decline.DISCUSSIONp‐tau217 stands out among markers for its strong association with disease and cognitive decline, indicating its potential for early AD detection and monitoring progression.HIGHLIGHTS Phosphorylated‐tau217 (p‐tau217) trajectories were significantly different in people who were known to be amyloid positive. Subtle age‐related trajectories were seen for all the plasma markers in amyloid‐negative cognitively unimpaired. Kidney function and body mass index were not associated with plasma p‐tau217 trajectories. Higher plasma p‐tau217 was associated with faster preclinical cognitive decline.