CSF VEGF Was Positively Associated with Neurogranin Independent of [beta]-Amyloid Pathology

Purpose: Increasing evidence suggests that both vascular endothelial growth factor (VEGF) and synaptic failure have been involved in the pathogenesis of Alzheimer's disease (AD). However, it is not clear whether CSF VEGF levels are associated with synaptic function in living human. Patients and Methods: In the present study, we included a total of 291 older individuals, including 83 individuals with normal cognition (NC), 143 individuals with mild cognitive impairment (MCI) and 65 patients with AD. Several linear regression models were conducted to examine the associations of CSF VEGF with CSF neurogranin levels (NG, reflecting synaptic degeneration) when controlling for other potential confounding factors, including age, gender, years of education, clinical diagnosis, APOE4 genotype and CSF [beta]-amyloid 42 (A[beta] 42) levels. Results: There was no significant difference in VEGF levels between the three diagnostic groups. In the pooled sample, females had significantly lower levels of VEGF than males. A[beta]-positive (CSF A[beta] 42 < 192 pg/mL) individuals had lower levels of VEGF than A[beta]-negative individuals. However, the relationships between VEGF and NG levels were not modified by disease stage. Finally, we found that CSF VEGF levels were associated with NG levels with adjustment of age, gender, years of education, clinical diagnosis, APOE4 genotype and CSFA[beta] 42 levels. Conclusion: CSF VEGF levels were associated with NG independent of AD pathology and disease stage. Keywords: vascular endothelial growth factor, neurogranin, synaptic dysfunction, Alzheimer's disease