Synaptic markers are associated with cognitive decline after accounting for amyloid burden among an at-risk Alzheimer's disease cohort.
Level 3 - non-randomized controlled study
Longitudinal observational cohort study evaluating prognostic biomarkers.
PubMed 40461705 · doi:10.1038/s41598-025-04319-3
What was done
Analyzed longitudinal cognitive decline (measured using the Preclinical Alzheimer's Cognitive Composite) alongside cerebrospinal fluid (CSF) biomarkers in 434 at-risk, predominantly unimpaired participants across two harmonized cohorts. Baseline CSF markers evaluated were amyloid-beta 42 (ab42) and phosphorylated tau 181 (p-tau181) to define amyloid positivity, alongside neurofilament light, neurogranin, SNAP-25, and NPTX2.
What was found
The abstract reports directional relationships without numerical effect sizes, variance estimates, or p-values. Most neurodegeneration markers were higher in amyloid-positive individuals and lower in cognitively unimpaired individuals, whereas NPTX2 showed the opposite pattern. Higher NPTX2 was associated with slower rates of cognitive decline even among amyloid-positive individuals. A combined SNAP-25/NPTX2 ratio explained more variance in cognitive decline than other individual biomarkers.
Why it matters
Demonstrates that markers of synaptic function—specifically NPTX2 and the SNAP-25/NPTX2 ratio—provide prognostic value for cognitive decline and resilience in preclinical Alzheimer's disease beyond amyloid burden.
Limits
The abstract provides no exact quantitative values, effect sizes, or confidence intervals. The sample is limited to at-risk, predominantly unimpaired individuals, which may not generalize to broader unselected populations or later dementia stages. Observational biomarker associations cannot establish causal mechanisms.