APOE ε4-specific associations of VEGF gene family expression with cognitive aging and Alzheimer's disease.

Moore AM, Mahoney E, Dumitrescu L, De Jager PL, Koran MEI, Petyuk VA, Robinson RA, Ruderfer DM, Cox NJ, Schneider JA, Bennett DA, Jefferson AL, Hohman TJ
Neurobiol Aging. 2020 87: 18-25

PMID: 31791659 · PMCID: PMC7064375 · DOI:10.1016/j.neurobiolaging.2019.10.021

Literature suggests vascular endothelial growth factor A (VEGFA) is protective among those at highest risk for Alzheimer's disease (AD). Apolipoprotein E (APOE) ε4 allele carriers represent a highly susceptible population for cognitive decline, and VEGF may confer distinct protection among APOE-ε4 carriers. We evaluated interactions between cortical expression of 10 VEGF gene family members and APOE-ε4 genotype to clarify which VEGF genes modify the association between APOE-ε4 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-ε4 on cognitive performance (p.fdr < 0.05). Higher NRP1 expression correlated with worse outcomes among ε4 carriers but better outcomes among ε4 noncarriers, suggesting NRP1 modifies the risk for poor cognitive scores based on APOE-ε4 status. NRP1 regulates angiogenesis, and literature suggests vessels in APOE-ε4 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 ε4 allele status.

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

MeSH Terms (16)

Aged Aged, 80 and over Aging Apolipoprotein E4 Cognitive Aging Cognitive Dysfunction Female Gene Expression Genetic Association Studies Genetic Predisposition to Disease Genotype Humans Male Neovascularization, Physiologic Neuropilin-1 Vascular Endothelial Growth Factor A

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