Understanding which early biological signals best forecast Alzheimer's disease progression is one of the most consequential questions in dementia prevention. The answer shapes when clinicians intervene, which patients enter trials, and whether plasma-based screening can meaningfully replace costly imaging — making this longitudinal analysis particularly relevant to the growing field of blood-based dementia risk stratification.
Drawing on 373 participants from the Alzheimer's Disease Neuroimaging Initiative, this analysis examined how baseline plasma biomarker values — and their rates of change over time — relate to downstream shifts in amyloid PET burden, cortical thickness, and cognitive performance. A consistent pattern emerged: static baseline measurements outperformed dynamic change metrics as predictors of disease trajectory. Phosphorylated tau 217 (p-tau217) stood out as the most broadly informative single marker. In amyloid PET-negative individuals, baseline p-tau217 and the Aβ42/Aβ40 ratio were most tightly linked to future amyloid accumulation rates, suggesting utility in pre-symptomatic staging. Among those already amyloid PET-positive, baseline p-tau217 was the dominant predictor of cortical thinning and cognitive decline speed.
This finding carries meaningful implications for trial design and clinical monitoring. The field has increasingly validated p-tau217 as a diagnostic signal, but this study reframes it as a prognostic tool — the level at a single time point may carry more information than trajectory alone. That said, the cohort of 373 is modest, the ADNI sample skews toward well-characterized research volunteers, and the non-parametric correlational design cannot establish causation. Replication in more diverse, population-representative cohorts is essential. Still, the demonstration that one affordable plasma draw could index multiple downstream disease rates is incrementally significant — and practically, suggests baseline p-tau217 may deserve prioritization in longitudinal monitoring frameworks even before amyloid pathology becomes PET-detectable.