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Association of apolipoprotein E ϵ2 and vasculopathy in cerebral amyloid angiopathy
Abstract
Objective Hemorrhage related to cerebral amyloid angiopathy (CAA) appears to occur through a multistep pathway that includes deposition of beta-amyloid in cerebral vessels and specific vasculopathic changes in the amyloid-laden vessels, such as cracking of the vessel wall. Recent reports suggest a positive association between CAA-related hemorrhage and both the apolipoprotein E (APOE) epsilon4 allele and, unexpectedly, the APOE epsilon2 allele. Unlike APOE epsilon4, APOE epsilon2 does not appear to act through increased beta-amyloid deposition. We therefore sought to determine whether it might specifically accelerate the second step in this pathway, that is, development of the vasculopathic changes that lead to hemorrhage. Methods To determine the role of APOE in development of vasculopathic changes, we compared APOE genotypes in two groups of postmortem brains: 52 brains with complete amyloid replacement of vessel walls but without vasculopathic changes, and 23 brains with complete amyloid replacement of vessels with the accompanying changes of cracking of the vessel wall and paravascular leaking of blood. Results Frequency of APOE epsilon2 was significantly greater in the group with vasculopathy (0.09) than the group without (0.01, p = 0.03). The groups did not differ in mean age or extent of neuritic plaques. Analysis of a clinical series of patients with CAA-related hemorrhage confirmed an overrepresentation of APOE epsilon2 as well as an association between this allele a…
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“However, human studies have linked APOE2 to greater CAA severity in some cohorts 52 , and to CAA-related vasculopathic changes and hemorrhagic complications 53,54 .”
From APOE2 attenuates APOE4-associated amyloid pathology and related toxicity in a mouse model of Alzheimer’s disease (2026) · cites this paper as [53]
In the citing paper
“Of note, APOEε2/ε4 individuals have a particularly high risk of intracerebral lobar haemorrhage in the presence of CAA50, possibly because the APOEε2 allele has been associated with fibrinoid necrosis of the vessel wall56,57.”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [56]
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Alzheimer’s Disease: The Challenge of the Second Century
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Metadata
- Authors
- Greenberg, S. M., Vonsattel, J.-P. G., Segal, A. Z., Chiu, R. I., Clatworthy, A. E., Liao, A., Hyman, B. T., & Rebeck, G. W.
- Affiliations
- Harvard University (US)
- Venue
- Neurology
- Published
- 1998-04
- Volume
- 50
- Issue
- 4
- Pages
- 961-965
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2041396523
- Cited by
- 267
- References
- 23
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 11 · 2023: 6 · 2022: 6 · 2021: 10 · 2020: 8 · 2019: 11 · 2018: 12 · 2017: 9 · 2016: 4 · 2015: 15 · 2014: 9 · 2013: 15 · 2012: 12
- FWCI
- 7.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chinese Academy of Agricultural Sciences
- National Institute on Aging (AG14473, AG 12406, AG00725)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Cerebrovascular and genetic disorders
- Keywords
- cerebral amyloid angiopathy, APOE ε4, intracerebral hemorrhage, vasculopathy, amyloid-beta deposition, postmortem brain
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Amyloidosis, Apolipoproteins E, Cerebral Arteries, Cerebral Hemorrhage, Genotype, Humans, Middle Aged, Cohort Studies, Apolipoprotein E2
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