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

The underlying mechanism of apolipoprotein E ε4 (APOE ε4) 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 ε4 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 Aβ42, and tau protein. We found that levels of SNAP-25 in CSF were substantially greater in APOE ε4 carriers compared to noncarriers with MCI. There was no significant difference in SNAP-25 levels between APOE ε4 carriers and noncarriers with normal cognition or AD. CSF SNAP-25 levels were associated with MMSE and CSF Aβ and tau levels. In summary, APOE ε4 may affect CSF SNAP levels in MCI patients, suggesting an important role of APOE ε4 in synaptic dysfunction leading to AD.