Apolipoprotein E epsilon4 is associated with atrophy of the amygdala in Alzheimerʹs disease

Although the ApoE epsilon (Porson)4 allele is well-established as the most important genetic risk factor for Alzheimerʹs 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 (Porson)4+ AD patients, 23 epsilon (Porson)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 (Porson)4+ than epsilon (Porson)4− AD patients, controlling for disease severity (F = 10.62; d.f. = 1,52; p = 0.002; ANCOVA). Alternatively, when ApoE epsilon (Porson)4 dose was considered, this effect appeared to accrue from a difference between the 0epsilon (Porson)4 and each of the other two AD groups, with no significant difference between the 1epsilon (Porson)4 and 2epsilon (Porson)4 AD groups. Hippocampal volumes and asymmetry indices for hippocampus and amygdala did not differ between epsilon (Porson)4 carriers and noncarriers. These results suggest accelerated atrophy of the amygdala in AD in association with ApoE epsilon (Porson)4 and provide further evidence for regionally specific effects of this allele.