JMIR Publications

ABSTRACT

Synaptic loss is the best surrogate for cognitive decline in Alzheimer disease (AD) and is more closely associated with cognitive function that amyloid or tau pathologies. Neurogranin (Ng) and synaptosomal-associated protein-25 (SNAP-25) have demonstrated utility as cerebrospinal fluid (CSF) markers of synaptic injury in pre-symptomatic and symptomatic AD. While these synaptic markers have been shown to correlate with cognitive impairment and whole brain or regional atrophy in previous studies of AD, to our knowledge- the relationship between fluid markers of synaptic injury and functional brain imaging has not been previously investigated. We here aim to examine the relationship between CSF markers of synaptic injury and functional connectivity (FC) in the default-mode and semantic memory networks in a cross-sectional study which includes individuals with very mild and mild AD (Clinical Dementia Rating [CDR] 0.5-1, n=15) and cognitively normal controls (CDR 0, n=15). We hypothesize that higher CSF Ng and SNAP-25 levels, reflective of more severe synaptic injury, will be associated with lower FC in the default-mode and semantic memory networks in individuals with AD but not in cognitively normal controls. Findings from this study will validate the utility of CSF Ng and SNAP-25 as markers of synaptic injury by examining their associations with functional alterations in important cortical networks involved in early AD.