Cerebral amyloid angiopathy-related hemorrhage: Interaction of APOE ε2 with putative clinical risk factors

Mark O. McCarron, James A R Nicoll, James W. Ironside, Seth Love, Mark J. Alberts, Ian Bone

Research output: Contribution to journalArticlepeer-review

83 Scopus citations


Background and Purpose - Current evidence suggests that the apolipoprotein E (APOE for gene; apoE for protein) ε4 allele predisposes to cerebral amyloid angiopathy (CAA) whereas ε2 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 ε2 allele. Antiplatelet or anticoagulant medication, hypertension, or minor head trauma were significantly more frequent antecedents of CAAH in ε2 carriers than in non-ε2 carriers (81% versus 35%, P=0.008), antiplatelet/anticoagulant medication in particular (P=0.038). Conclusions - Our findings suggest that antiplatelet or anticoagulant medication, hypertension, or minor head trauma are most likely to precipitate cerebral hemorrhage in patients with CAA who are also ε2 carriers. This may result from isoform-specific effects of apoE on the structure of amyloid-laden blood vessel walls.

Original languageEnglish (US)
Pages (from-to)1643-1646
Number of pages4
Issue number8
StatePublished - Aug 1999


  • Apolipoproteins
  • Cerebral amyloid angiopathy
  • Intracerebral hemorrhage

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing


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