APOE gene polymorphism as a risk factor for cerebral amyloid angiopathy-related hemorrhage

Cerebral amyloid angiopathy (CAA) due to the accumulation of amyloid beta-protein (Abeta) occurs in up to half of elderly individuals and in most cases of Alzheimer's disease (AD). Following identification of the apolipoprotein E (APOE) epsilon4 allele as a risk factor for AD, APOE epsilon4 was also found to be associated with asymptomatic CAA. The major clinical manifestation of CAA is stroke due to a lobar hemorrhage. A complex relationship between APOE epsilon4, APOE epsilon2 and hemorrhage associated with CAA (CAAH) is emerging. Pathological studies have demonstrated that APOE epsilon2 is over-represented among patients with CAAH. This remains the case for patients with co-existing Alzheimer's disease, who otherwise have a very low epsilon2 allele frequency. Other forms of intracranial hemorrhage do not share the same association, indicating that APOE epsilon2 has a specific association with CAAH. Patients with the epsilon2 allele and CAAH are more likely to have taken anticoagulant or antiplatelet medication, had hypertension or had minor head trauma than non-epsilon2 carriers. In addition, the epsilon2 allele is specifically associated with CAA-associated microangiopathic changes such as fibrinoid necrosis and concentric splitting of the vessel wall.