Abstract
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 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. Results: 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. Discussion: APOE differentially affects type and timing of CVD-related neuropathology.
Original language | English (US) |
---|---|
Pages (from-to) | 258-266 |
Number of pages | 9 |
Journal | Alzheimer's and Dementia |
Volume | 15 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2019 |
Keywords
- APOE ε2 allele
- APOE ε4 allele
- Cerebrovascular disease
- Neuropathology
- Oldest old
ASJC Scopus subject areas
- Clinical Neurology
- Geriatrics and Gerontology
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Health Policy
- Developmental Neuroscience
- Epidemiology