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Alzheimers Dement. 2019 Feb;15(2):258-266. doi: 10.1016/j.jalz.2018.08.007. Epub 2018 Oct 12.

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

Author information

1
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Behavioral Sciences, Rush University Medical Center, Chicago, IL, USA. Electronic address: melissa_lamar@rush.edu.
2
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
3
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
4
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA.
5
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Behavioral Sciences, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
6
Department of Geriatrics, University of Sao Paulo Medical School, Sao Paulo, Brazil.
7
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; Department of Pathology, Rush University Medical Center, Chicago, IL, USA.

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.

KEYWORDS:

APOE ε2 allele; APOE ε4 allele; Cerebrovascular disease; Neuropathology; Oldest old

PMID:
30321502
PMCID:
PMC6368888
[Available on 2020-02-01]
DOI:
10.1016/j.jalz.2018.08.007

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