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Cited by 27Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCerebrovascular and genetic disorders

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

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Lamar, Melissa, Yu, Lei, Rubin, Leah H., James, Bryan D., Barnes, Lisa L., Farfel, Jose Marcelo, Gaiteri, Chris, Buchman, Aron S. +2 more·2019·Alzheimer's & Dementia
DOI 10.1016/j.jalz.2018.08.007PMC PMC6368888
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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.

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  • Relative to APOEε3 homozygotes, APOEε2/ε4 carriers have greater Aβ plaque burden, increased cerebral amyloid angiopathy severity and increased odds of macroinfarcts, whereas differences in tangle burden are conflicting.

    “However, relative to APOEε3 homozygotes, APOEε2/ε4 carriers have greater Aβ plaque burden54, increased CAA severity50 and increased odds of macroinfarcts55, whereas differences in tangle burden are conflicting49,54.”

    From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [55]

  • APOEε2 is associated with more severe ischaemic small vessel disease in the form of arteriolosclerosis, especially in individuals aged 90 years and older.

    “whereas APOEε2 is associated with more severe ischaemic small vessel disease in the form of arteriolosclerosis, especially in individuals aged 90 years and older55.”

    From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [55]

  • Compared with APOEε3 homozygosis, APOEε4 carriage has been independently associated with increased cerebrovascular burden in the form of gross macro infarcts in some studies, but not others.

    “Compared with APOEε3 homozygosis, APOEε4 carriage has been independently associated with increased cerebrovascular burden in the form of gross (macro) infarcts in some studies55, but not others50, whereas APOEε2 is associated with more severe ischaemic small vessel disease in the form of arteriolosclerosis, especially in individuals aged 90 years and older55.”

    From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [55]

  • Neither APOEε4 nor APOEε2 is associated with atherosclerosis in the circle of Willis or microinfarcts.

    “Neither allele is associated with atherosclerosis in the circle of Willis or microinfarcts55.”

    From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [55]

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Cited by

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Authors
Lamar, M., Yu, L., Rubin, L. H., James, B. D., Barnes, L. L., Farfel, J. M., Gaiteri, C., Buchman, A. S., Bennett, D. A., & Schneider, J. A.
Affiliations
  • Rush University Medical Center (US)
  • Johns Hopkins University (US)
  • Department of Geriatrics University of Sao Paulo Medical School Sao Paulo Brazil
Corresponding author
Lamar, Melissa
ORCID
Venue
Alzheimer's & Dementia
Publisher
Wiley
Published
2018-10-12
Volume
15
Issue
2
Pages
258-266
ISSN
  • 1552-5260 (ISSN-L)
  • 1552-5279
DOI
10.1016/j.jalz.2018.08.007
PMC
PMC6368888
OpenAlex
W2897580574
Cited by
27
References
6
Citations by year
2026: 2 · 2025: 3 · 2024: 7 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 4
FWCI
1.37
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Alzheimer s & Dementia (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • Institute on Aging, College of Medicine, University of Florida (R01 AG043379, P30 AG10161, RF1 AG22018, R01 AG15819, R01 AG24480, K01 AG040192)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
Keywords
apolipoprotein E, APOE ε4
MeSH terms
Aged, Aged, 80 and over, Alleles, Alzheimer Disease, Apolipoproteins E, Cerebrovascular Disorders, Female, Genotype, Heterozygote, Humans, Male, Risk Factors, Genetic Predisposition to Disease

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