APOLIPOPROTEIN-E EPSILON-4 IS ASSOCIATED WITH THE PRESENCE AND EARLIER ONSET OF HEMORRHAGE IN CEREBRAL AMYLOID ANGIOPATHY

Background and Purpose Cerebral amyloid angiopathy is an important cau se of intracerebral hemorrhage in the elderly. The epsilon 4 allele of the apolipoprotein E gene, recently established as a genetic risk for Alzheimer's disease, has also been suggested as a possible risk facto r for cerebral amyloid angiopathy. We sought to determine whether this allele is specifically associated with hemorrhages related to amyloid angiopathy and whether it correlates with the age at which first amyl oid angiopathy-related hemorrhage occurs. Methods Forty-five consecuti ve patients presenting with lobar hemorrhage were prospectively classi fied according to clinical, radiological, and when available, patholog ical features and evaluated for apolipoprotein E genotype. They were c ompared with 1899 elderly patients from a population-based sample and with 18 consecutive patients with hemorrhages in deep regions typical of a hypertensive mechanism. Results Patients with multiple hemorrhage s confirmed to the lobar territory demonstrated a greater than twofold overrepresentation (P<.001) in frequency of the apolipoprotein E epsi lon 4 allele compared with the population-based sample. Apolipoprotein E genotypes of patients with hemorrhages in deep territories resemble d the population sample. Among patients with strictly lobar hemorrhage s, carriers of the epsilon 4 allele had their first hemorrhage more th an 5 years earlier than noncarriers (mean age at first hemorrhage, 73. 4 +/- 8.0 versus 78.9 +/- 7.4 years; P = .033). These effects were ind ependent of the accompanying presence of Alzheimer's disease. Conclusi ons The data support a specific role for apolipoprotein E epsilon 4 in accelerating the process that leads to amyloid angiopathy-related hem orrhage.