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

Although the ApoE epsilon 4 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 epsilon 4+ AD patients, 23 epsilon 4- AD patients, and 42 cognitively normal elderly control subjects. Analysis of covariance revealed that amygdaloid volume was significantly smaller (19.2%) in ApoE epsilon 4+ than epsilon 4- AD patients, controlling for disease severity (F = 10.62; d.f. = 1,52; p = 0.002; ANCOVA). Alternatively, when ApoE epsilon 4 dose was considered, this effect appeared to accrue from a difference between the 0 epsilon 4 and each of the other two AD groups, with no significant difference between the 1 epsilon 4 and 2 epsilon 4 AD groups. Hippocampal volumes and asymmetry indices for hippocampus and amygdala did not differ between epsilon 4 carriers and noncarriers. These results suggest accelerated atrophy of the amygdala in AD in association with ApoE epsilon 4 and provide further evidence for regionally specific effects of this allele. (c) 2005 Elsevier Inc. All rights reserved.