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

Introduction: 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. Methods: 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 epsilon 2/epsilon 4 carriers, multivariable regressions for each CVD-related neuropathology compared epsilon 4 and epsilon 2 carriers to epsilon 3/epsilon 3 carriers adjusting for confounders including age and Alzheimer's neuropathology. Results: Three hundred forty-two individuals (24.7%; similar to 87.7 years at death; 39.9% nondemented) were epsilon 3/epsilon 4 or epsilon 4/epsilon 4, and 180 (13.0%; similar to 89.9 years at death; 66.6% nondemented) were epsilon 2/epsilon 3 or epsilon 2/epsilon 2. epsilon 4 carriers had higher odds of macroinfarcts (odds ratio = 1.41, 95% confidence interval: 1.02-1.94, P = .03), whereas epsilon 2 carriers had higher odds of moderate-to-severe arteriolosclerosis (odds ratio = 1.68, 95% confidence interval: 1.15-2.45, P = .006) compared to e3/e3 carriers. Age-stratified analyses suggested that these relationships were driven by epsilon 4 carriers <90 years at death and epsilon 2 carriers >= 90 years at death, respectively. Discussion: APOE differentially affects type and timing of CVD-related neuropathology. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.