Plasma biomarkers and incident clinical stage progression in the specialized memory clinic: a longitudinal study

INTRODUCTION: The utility of blood‑based Alzheimer's disease (AD) biomarkers in predicting clinical trajectories remains uncertain. METHODS: We assessed the diagnostic and prognostic performance of p-tau181, p-tau217, GFAP, and NfL in a large memory‑clinic cohort (n=3,645) with comprehensive baseline clinical evaluation and annual follow‑up for up to three decades. RESULTS: P-tau217, p-tau181 and GFAP were associated with amyloid-beta (Aβ) pathology, while all biomarkers were elevated in AD and all-cause dementia. P-tau217 significantly outperformed others in detecting Aβ pathology and clinical AD but performed similarly to NfL and GFAP for all-cause dementia. Prognostically, p‑tau217 demonstrated the strongest association with cognitive decline, followed by GFAP and NfL, and best predicted progression status at 5‑ and 10‑year intervals. All biomarkers provided added prognostic value beyond demographic and genetic covariates. DISCUSSION: These findings support plasma biomarkers for disease identification and risk stratification while underscoring the need for population‑specific approaches.