Cerebrospinal Fluid Synaptosomal-Associated Protein 25 Levels in Patients with Alzheimer's Disease: A Meta-Analysis

Background: Several studies have shown increased levels of cerebrospinal fluid (CSF) synaptosomal-associated protein 25 (SNAP-25) in patients with Alzheimer's disease (AD). However, results have been inconsistent thus far. Objective: We conducted meta-analyses summarizing the associations of CSF SNAP-25 levels with AD to assess the utility of SNAP-25 as a novel biomarker for AD. Methods: We conducted a meta-analysis of differences in CSF SNAP-25 levels in patients with AD or mild cognitive impairment (MCI) and in cognitively healthy controls (HC). We calculated pooled correlation coefficients comparing SNAP-25 levels and total tau (T-tau) or hyperphosphorylated tau (P-tau) in CSF. Results: Eight studies enrolling 1,162 individuals (423 AD, 275 MCI, 464HC) were included for quantitative analysis. Patients with AD (ratio of means [RoM] = 1.50, 95% confidence interval [CI]: 1.30, 1.74) and MCI (RoM = 1.45, 95% CI: 1.12, 1.87) had increased levels of CSF SNAP-25 as compared to HC. The difference in CSF SNAP-25 levels when comparing AD and MCI (RoM = 1.05, 95% CI: 0.96, 1.14) was not statistically significant but showed a trend toward significance. Statistically significant correlations were found when comparing CSFSNAP-25 with CSF T-tau (Spearman correlation coefficient, rho=0.78; rho=0.66; rho=0.69, respectively) and P-tau (rho=0.77; rho=0.70; rho=0.62, respectively) levels in patients with AD, MCI, and HC. Conclusion: Increased CSF SNAP-25 levels differentiated patients with AD or MCI from controls, suggesting the utility of this biomarker in the early diagnosis of AD.