APOE genotypes as a risk factor for age-dependent accumulation of cerebrovascular disease in older adults.

Apolipoprotein E (APOE) is a susceptibility gene for late-onset Alzheimer's disease neuropathology; less is known about the relationship between APOE and cerebrovascular disease (CVD) neuropathology. We investigated associations of APOE status with arteriolosclerosis, macroinfarcts and microinfarcts, and atherosclerosis in 1383 adults (65.9-108.2 years at death) with and without dementia. Excluding ε2/ε4 carriers, multivariable regressions for each CVD-related neuropathology compared ε4 and ε2 carriers to ε3/ε3 carriers adjusting for confounders including age and Alzheimer's neuropathology. Three hundred forty-two individuals (24.7%; ∼87.7 years at death; 39.9% nondemented) were ε3/ε4 or ε4/ε4, and 180 (13.0%; ∼89.9 years at death; 66.6% nondemented) were ε2/ε3 or ε2/ε2. ε4 carriers had higher odds of macroinfarcts (odds ratio = 1.41, 95% confidence interval: 1.02-1.94, P = .03), whereas ε2 carriers had higher odds of moderate-to-severe arteriolosclerosis (odds ratio = 1.68, 95% confidence interval: 1.15-2.45, P = .006) compared to ε3/ε3 carriers. Age-stratified analyses suggested that these relationships were driven by ε4 carriers <90 years at death and ε2 carriers ≥90 years at death, respectively. APOE differentially affects type and timing of CVD-related neuropathology. Copyright © 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Citation

Melissa Lamar, Lei Yu, Leah H Rubin, Bryan D James, Lisa L Barnes, Jose Marcelo Farfel, Chris Gaiteri, Aron S Buchman, David A Bennett, Julie A Schneider. APOE genotypes as a risk factor for age-dependent accumulation of cerebrovascular disease in older adults. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2019 Feb;15(2):258-266

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PMID: 30321502

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