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.
Nicoll
J A
JA
Department of Neuropathology, University of Glasgow, Institute of Neurological Sciences, Southern General Hospital, UK. J.Nicoll@clinmed.gla.ac.uk
McCarron
M O
MO
D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics; D053329:Apolipoprotein E2; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D016657:Cerebral Amyloid Angiopathy / Q000209:etiology* / Q000235:genetics*; D002543:Cerebral Hemorrhage / Q000209:etiology* / Q000235:genetics*; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic; D012307:Risk Factors
D053329:Apolipoprotein E2; D053327:Apolipoprotein E4; D001057:Apolipoproteins E