Apolipoprotein E epsilon 4 and cerebral hemorrhage associated with amyloid angiopathy

Ann Neurol. 1995 Aug;38(2):254-9. doi: 10.1002/ana.410380219.


Cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular deposition of the amyloid beta-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 epsilon 4 (apoE epsilon 4) allele was associated with CAA and hemorrhage and whether this association was independent of Alzheimer's disease. The apoE epsilon 4 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 epsilon 4 increased the odds ratio for moderate or severe CAA by 2.9-fold, relative to cases without epsilon 4; two copies of epsilon 4 increased the odds ratio 13.1-fold. In the cohort of CAA-associated cerebral hemorrhages, the apoE epsilon 4 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 epsilon 4 is a risk factor for CAA and CAA-related hemorrhage, independent of its association with Alzheimer's disease.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Apolipoproteins E / metabolism
  • Base Sequence
  • Cerebral Amyloid Angiopathy / complications
  • Cerebral Amyloid Angiopathy / genetics*
  • Cerebral Amyloid Angiopathy / metabolism
  • Cerebral Amyloid Angiopathy / pathology
  • Cerebral Hemorrhage / etiology
  • Cerebral Hemorrhage / genetics*
  • Cerebral Hemorrhage / metabolism
  • Dementia / pathology
  • Genotype
  • Humans
  • Middle Aged
  • Molecular Sequence Data


  • Apolipoprotein E4
  • Apolipoproteins E