APOE ε4 is associated with higher levels of CSF SNAP-25 in prodromal Alzheimer's disease

The underlying mechanism of apolipoprotein E epsilon 4 (APOE epsilon 4) in the pathogenesis of Alzheimer's disease (AD) remains elusive. We hypothesize that synaptic function is differentially affected by APOE isoforms. Levels of CSF SNAP-25 were compared between APOE epsilon 4 carriers and noncarriers in 55 participants with normal cognition, 75 patients with mild cognitive impairment (MCI), and 16 patients with mild AD dementia. We investigated relationships between SNAP-25 levels and age, gender, education, CSF A beta 42, and tau protein. We found that levels of SNAP-25 in CSF were substantially greater in APOE epsilon 4 carriers compared to noncarriers with MCI. There was no significant difference in SNAP-25 levels between APOE epsilon 4 carriers and noncarriers with normal cognition or AD. CSF SNAP-25 levels were associated with MMSE and CSF A beta and tau levels. In summary, APOE epsilon 4 may affect CSF SNAP levels in MCI patients, suggesting an important role of APOE epsilon 4 in synaptic dysfunction leading to AD.