Apolipoprotein E epsilon4 is associated with atrophy of the amygdala in Alzheimer's disease.

Although the ApoE epsilon4 allele is well-established as the most important genetic risk factor for Alzheimer's disease (AD), the effects of this allele on regional brain atrophy in AD patients remain controversial. We performed MRI-based volumetric measurements of the hippocampus and amygdala (normalized to intracranial volume) in 32 epsilon4+ AD patients, 23 epsilon4- AD patients, and 42 cognitively normal elderly control subjects. Analysis of covariance revealed that amygdaloid volume was significantly smaller (19.2%) in ApoE epsilon4+ than epsilon4- AD patients, controlling for disease severity (F = 10.62; d.f. = 1,52; p = 0.002; ANCOVA). Alternatively, when ApoE epsilon4 dose was considered, this effect appeared to accrue from a difference between the 0epsilon4 and each of the other two AD groups, with no significant difference between the 1epsilon4 and 2epsilon4 AD groups. Hippocampal volumes and asymmetry indices for hippocampus and amygdala did not differ between epsilon4 carriers and noncarriers. These results suggest accelerated atrophy of the amygdala in AD in association with ApoE epsilon4 and provide further evidence for regionally specific effects of this allele.