The lack of a correlation between plasma pTau181 and VAMP2 (or SNAP25) in the presence of subthreshold Alzheimer’s disease pathology in some participants may suggest that their associations differ between plasma and CSF, potentially reflecting differences in the timing of detectable changes in synaptic proteins versus pTau, or in their Alzheimer specificity across biofluids. Here, SNAP25 is linked to Alzheimer disease.