Combined with the data from this study, we hypothesize that CSF VAMP-2, as well as SNAP-25 and Ng, partially reflect at least two separate mechanisms: (i) synaptic dysfunction with low concentration at normal/low p-tau levels (A + ,T −) which could either be considered a general early-stage process or a process related to a specific biological AD subtype with low p-tau and (ii) tau-mediated neuronal loss which leads to higher concentrations due to release into the CSF. This evidence concerns the gene SNAP25 and Alzheimer disease.