Work

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

Year: 2019

Type: article

Abstract: 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.

Source: Neurobiology of Aging

DOI: 10.1016/j.neurobiolaging.2019.10.021

Authors: Annah M. Moore, Emily Mahoney, Logan Dumitrescu, Philip L. De Jager, Mary Ellen I. Koran, Vladislav A. Petyuk, Renã AS. Robinson, Douglas M. Ruderfer, Nancy J. Cox, Julie A. Schneider, David A. Bennett, Angela L. Jefferson, Timothy J. Hohman

Institutions: Vanderbilt University, Vanderbilt University Medical Center, Broad Institute, Columbia University Irving Medical Center, Columbia University, Stanford Health Care, Stanford Medicine, Stanford University, Pacific Northwest National Laboratory, Rush University Medical Center

Language: English

Topic: Dementia and Cognitive Impairment Research

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,200

Funders: Vanderbilt University, National Institutes of Health, National Institute on Aging, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development

Awards: G1513904913, Genetic Drivers of Resilience to Alzheimer's Disease, G3743240706, Pathway discovery, validation and compound identification for Alzheimer's disease, G3970733997, G4019563118, G4278927122, Neuroprotective Effects of Vascular Endothelial Growth Factor in Alzheimer's Disease, G4421368135, G4425699080, Risk Factors, Pathology, and Clinical Expressions of AD, Genetic Resilience to the Clinical Manifestation of Dementia, Building Interdisciplinary Research Careers in Women's Health, G734120740, The Vanderbilt Institute for Clinical and Translational Research (VICTR), G828200374, Vanderbilt Interdisciplinary Training Program in Alzheimer's Disease, Vanderbilt Memory & Aging Project, G983864884

OpenAlex ID: W2986773415

FWCI: 3.154

Cites: 72

Cited by: 37

Related to: 10