The apolipoprotein E epsilon 2 allele and the pathological features in cerebral amyloid angiopathy-related hemorrhage

Cerebral amyloid angiopathy (CAA) is associated with apolipoprotein E (APOE gene, apoE protein) polymorphism: current evidence suggests that the epsil on 4 allele is a risk factor for the development of CAA and the epsilon 2 a llele predisposes to hemorrhage. We sought to determine the relationship be tween the APOE epsilon 2 allele and both the immunoreactivity profiles and vascular complications of CAA. We performed immunohistochemistry for amyloi d beta-protein (A beta), apoE, cystatin C, and activated microglia, and exa mined the morphology of cortical and leptomeningeal vessels in 37 CAA-relat ed hemorrhage (CAAH), 26 Alzheimer disease (AD) patients, and 20 controls. The extent of immunostaining of vessels for A beta, apoE, cystatin C, and p erivascular activated microglia increased from controls through AD to a max imum in CAAH patients. Among cases with CAA (37 CAAH, 19 AD, and 6 controls , n = 62) vascular apoE (p < 5 X 10(-4)), cystatin C (p < 10(-4)), activate d microglia (p < 10(-4)), vessels with a high ratio of wall thickness to lu men diameter (p < 0.003) as well as dilated/microaneurysmal vessels (p < 0. 01) were present more frequently in patients with hemorrhage than without; however, these features were not associated with the APOE epsilon 2 allele. Fibrinoid necrosis alone was associated with the APOE epsilon 2 allele (p < 0.04) and we suggest that over-representation of APOE epsilon 2 in CAAH m ay result from its association with fibrinoid necrosis.