Cerebral Amyloid Angiopathy–Related Hemorrhage: Interaction of APOE ε2 With Putative Clinical Risk Factors
Abstract
Background and purpose Current evidence suggests that the apolipoprotein E (APOE for gene; apoE for protein) epsilon4 allele predisposes to cerebral amyloid angiopathy (CAA) whereas epsilon2 is associated with CAA-related hemorrhage (CAAH). The clinical risk factors for other forms of intracranial hemorrhage are a less-frequent feature of CAAH. In this study we examined potential clinical risk factors in patients with CAAH and assessed these with respect to APOE genotype. Methods Thirty-six patients were identified with a pathological diagnosis of CAAH. Clinical notes were reviewed to document age of hemorrhage onset, history of dementia, antiplatelet/anticoagulant medication, hypertension, minor head trauma, or transient neurological events. In a review of reported cases of CAAH, the frequency of these clinical features was also recorded. APOE genotypes were determined with use of polymerase chain reaction techniques. Results There were 24 women and 12 men; the mean age was 70.3 years. One third (n=12) had been taking antiplatelet medication, and a similar number were demented. Nine patients were hypertensive, and 4 had a history of recent minor head trauma. The relative frequency of each of these clinical features was similar to that in previous reports. Forty-four percent (16 of 36) possessed an epsilon2 allele. Antiplatelet or anticoagulant medication, hypertension, or minor head trauma were significantly more frequent antecedents of CAAH in epsilon2 carriers than in non-…
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Evidence independently supports link of both the APOE ε4 and ε2 allele with increased risk for microhemorrhages in humans.
“Evidence independently supports link of both the APOE ε4 and ε2 allele with increased risk for microhemorrhages in humans [51, 52, 54–57].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [55]
Several human autopsy studies have shown that the ε2 allele is an exacerbating factor of microhemorrhages among subjects with VAβ pathology and that this effect is linked to fibrinoid necrosis of vascular wall specifically associated with the ε2 allele.
“Several human autopsy studies have shown that the ε2 allele is an exacerbating factor of microhemorrhages among subjects with VAβ pathology and that this effect is linked to fibrinoid necrosis of vascular wall specifically associated with the ε2 allele [55–57].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [55]
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- Authors
- McCarron, M. O., Nicoll, J. A. R., Ironside, J. W., Love, S., Alberts, M. J., & Bone, I.
- Affiliations
- Duke University (US)
- Venue
- Stroke
- Published
- 1999-08
- Volume
- 30
- Issue
- 8
- Pages
- 1643-1646
- ISSN
- 0039-2499 (ISSN-L)
- 1524-4628
- OpenAlex
- W2055763065
- Cited by
- 92
- References
- 60
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 1 · 2023: 3 · 2022: 1 · 2018: 1 · 2017: 3 · 2016: 4 · 2015: 10 · 2014: 5 · 2012: 3
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Stroke (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Chinese Academy of Agricultural Sciences
- Topics
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Health Sciences › Medicine › Neurology › Intracranial Aneurysms: Treatment and Complications
- Keywords
- cerebral amyloid angiopathy, APOE genotype, antiplatelet agents, anticoagulants, hypertension, mild traumatic brain injury, dementia, clinical risk factors, intracranial hemorrhage
- MeSH terms
- Aged, Aged, 80 and over, Apolipoproteins E, Biopsy, Brain, Cerebral Hemorrhage, Female, Genetic Markers, Genotype, Craniocerebral Trauma, Humans, Hypertension, Male, Middle Aged, Retrospective Studies, Risk Factors, Polymerase Chain Reaction, Cerebral Amyloid Angiopathy, Apolipoprotein E2
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