Apoe Epsilon 4-Specific Associations Of Vegf Gene Family Expression With Cognitive Aging And Alzheimer'S Disease

Literature suggests vascular endothelial growth factor A (VEGFA) is protective among those at highest risk for Alzheimer's disease (AD). Apolipoprotein E (APOE) epsilon 4 allele carriers represent a highly susceptible population for cognitive decline, and VEGF may confer distinct protection among APOE-epsilon 4 carriers. We evaluated interactions between cortical expression of 10 VEGF gene family members and APOE-epsilon 4 genotype to clarify which VEGF genes modify the association between APOE-epsilon 4 and cognitive decline. Data were obtained from the Religious Orders Study and Rush Memory and Aging Project (N = 531). Linear regression assessed interactions on global cognition. VEGF genes NRP1 and VEGFA interacted with APOE-epsilon 4 on cognitive performance (p.fdr < 0.05). Higher NRP1 expression correlated with worse outcomes among epsilon 4 carriers but better outcomes among epsilon 4 noncarriers, suggesting NRP1 modifies the risk for poor cognitive scores based on APOE-epsilon 4 status. NRP1 regulates angiogenesis, and literature suggests vessels in APOE-epsilon 4 brains are more prone to leaking, perhaps placing young vessels at risk for ischemia. Results suggest that future therapeutics targeting brain angiogenesis should also consider epsilon 4 allele status. (C) 2019 The Author(s). Published by Elsevier Inc.