Tracking clinical and neuroimaging progression of Alzheimer's disease by longitudinal trajectories of plasma biomarkers

INTRODUCTION: Blood biomarkers reflecting clinical and neuroimaging progression are essential to monitor Alzheimer's disease (AD). METHODS: In a 2-year prospective study of 94 early AD patients, four consecutive blood samples were collected and analyzed for phosphorylated tau217 (p-tau217), neurofilament light chain (NfL), brain-derived tau (BD-tau), and glial fibrillary acidic protein (GFAP). Linear mixed models were used to compare plasma biomarker trajectories between clinically stable and progressors, and to assess correlations with individual changes in Clinical Dementia Rating scale Sum of Boxes (CDR-SB), magnetic resonance imaging volumes, and [¹⁸F]-fluorodeoxyglucose positron emission tomography glucose metabolism. RESULTS: Plasma p-tau217 and the p-tau217/BD-tau ratio showed steeper trajectories in progressors. No plasma biomarkers correlated with individual clinical or neuroimaging changes, except for the p-tau217/BD-tau ratio, which weakly correlated with CDR-SB changes. Most plasma biomarker changes from baseline to follow-up remained within reference change values. DISCUSSION: Plasma p-tau217 increases more rapidly in clinical progressors, reflecting tau-related neurodegeneration underlying cognitive decline. The absence of a clear relationship with individual clinical measures suggests biomarker variability may mask disease-specific changes.