Cited by 151Intracerebral and Subarachnoid Hemorrhage ResearchAlzheimer's disease research and treatmentsCerebrovascular and genetic disorders

APOE-ε2 and APOE-ε4 Correlate With Increased Amyloid Accumulation in Cerebral Vasculature

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Nelson, Peter T., Pious, Nina M., Jicha, Gregory A., Wilcock, Donna M., Fardo, David W., Estus, Steven, Rebeck, G. William·2013·Journal of Neuropathology & Experimental Neurology

Abstract

The APOE-ε4 allele correlates with increased risk of Alzheimer disease (AD) and increased parenchymal amyloid plaques. We tested how the APOE genotype correlated with cerebral amyloid angiopathy (CAA) by analyzing 371 brains for parenchymal and meningeal CAA in 4 brain regions (frontal, parietal, temporal, and occipital neocortex). The overall severity of CAA was highest in the occipital lobe. APOE-ε4/4 brains (n = 22) had the highest levels of CAA across regions. In the occipital lobe, nearly all APOE-ε4/4 cases were scored with the highest level of CAA (meninges, 95% of cases; parenchyma, 81%). In this brain region as in others, APOE-ε3/4 brains (n = 115) showed consistently less CAA than APOE-ε4/4 brains (meninges, 43%; parenchyma, 43%). APOE-ε3/3 brains (n = 182) showed even less CAA (meninges, 19%; parenchyma, 19%). Interestingly, APOE-ε2/3 cases (n = 42) had more CAA than APOE-ε3/3 (meninges, 44%; parenchyma, 32%), despite a reduced risk for AD in the APOE-ε2/3 individuals. APOE-ε4/4 brains also had the fewest regions without CAA, whereas APOE-ε3/3 brains had the most. Ordinal regression analyses demonstrated significant impacts of APOE-ε2 and APOE-ε4 on CAA at least in some brain regions. These data demonstrate that APOE genotype correlations with Aβ deposition in CAA only incompletely correspond to other AD-linked brain pathologies.

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Authors
Nelson, P. T., Pious, N. M., Jicha, G. A., Wilcock, D. M., Fardo, D. W., Estus, S., & Rebeck, G. W.
Affiliations
  • University of Kentucky (US)
  • Georgetown University (US)
Corresponding author
Rebeck, G. William
Venue
Journal of Neuropathology & Experimental Neurology
Published
2013-07
Volume
72
Issue
7
Pages
708-715
ISSN
  • 0022-3069 (ISSN-L)
  • 1554-6578
OpenAlex
W2046985190
Cited by
150
References
43
Citations by year
2026: 13 · 2025: 20 · 2024: 20 · 2023: 20 · 2022: 14 · 2021: 12 · 2020: 12 · 2019: 6 · 2018: 6 · 2017: 2 · 2016: 8 · 2015: 10 · 2014: 7
FWCI
5.29
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuropathology & Experimental Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Aging (P01AG030128, P30AG028383, R01AG035379)
Topics
  • Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
Keywords
APOE ε2, APOE ε4, APOE genotype, cerebral amyloid angiopathy, amyloid-beta deposition, Alzheimer's disease, occipital lobe, APOE ε3
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Blood Vessels, Cerebral Cortex, Female, Humans, Male, Logistic Models, Amyloid beta-Peptides, Cerebral Amyloid Angiopathy, Apolipoprotein E4, Apolipoprotein E2

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