Apolipoprotein E ϵ4 and cerebral hemorrhage associated with amyloid angiopathy

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Abstract
Cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular deposition of the amyloid β‐peptide, leading to intracerebral hemorrhage in severe cases. Other than rare familial cases, the only identified risks for CAA are advancing age and accompanying Alzheimer's disease. We tested whether the apolipoprotein E ϵ4 (apoE ϵ4) allele was associated with CAA and hemorrhage and whether this association was independent of Alzheimer's disease. The apoE ϵ4 genotype was determined without knowledge of the pathology for 93 postmortem cases systematically graded for severity of CAA and for 15 patients with CAA‐associated intracerebral hemorrhage. We found a significant and independent effect of the apoE genotype in both cohorts. Among the postmortem cases, the presence of apoE ϵ4 increased the odds ratio 13.1‐fold. In the cohort of CAA‐associated cerebral hemorrhages, the apoE ϵ4 allele frequency was 0.40, significantly greater than the control frequency of 0.14. The increase in CAA remained even after controlling for the presence of Alzheimer's disease, suggesting that apoE ϵ4 is a risk factor for CAA and CAA‐related hemorrhage, independent of its association with Alzheimer's disease.