Given that synaptic dysfunction and loss are probably the major causes of the loss of neuropil underlying hippocampal atrophy [12], we believe that SNAP-25/Aβ42 may be an independent novel biomarker for synaptic pathology in AD, and the clinical manifestations of cognitive impairment and later dementia appear after neuronal injury and synaptic loss has reached a threshold in vulnerable brain regions. Here, SNAP25 is linked to hippocampal atrophy.