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Apolipoprotein E Genotype and Cerebral Amyloid Angiopathy‐related Hemorrhage

Abstract: Following the identification of the role of the apolipoprotein E (APOE) gene polymorphism in Alzheimer's disease (AD), this gene was examined in cerebral amyloid angiopathy (CAA). As in AD, the APOEɛ4 allele was found to be associated with CAA. Lobar intracerebral hemorrhage is the major clinical manifestation of CAA. Initial studies on a small number of patients with CAA‐related hemorrhage (CAAH) identified overrepresentation of APOEɛ4. However, it became clear that confounding bias from concomitant AD and the need for pathologically confirmed cases of CAAH would also have to be considered. A larger series of pathologically confirmed cases of CAAH, also assessed for AD pathology, found a surprising overrepresentation of the APOEɛ2 allele. Because of the association between CAA and AD, it might have been predicted that patients with CAAH would have a low, rather than a high, ɛ2 frequency. The overrepresentation of APOEɛ2 was present both in patients with and without AD, whereas a high ɛ4 frequency correlated with concomitant AD.