Hippocampal atrophy and apolipoprotein E genotype are independently associated with Alzheimer's disease

Abstract

A variety of anatomic and functional neuroimaging findings are associated with Alzheimer's disease (AD). One of the strongest imaging associations identified is between AD and hippocampal atrophy. The epsilon4 allele of the apolipoprotein E (ApoE) gene increases the risk of developing AD and lowers the mean age of onset of the disease. The purpose of this study was to assess the association between hippocampal volume and ApoE polymorphisms in elderly control subjects and in patients with probable AD. We performed magnetic resonance imaging-based volume measurements of the hippocampus in 125 cognitively normal elderly controls and 62 patients with probable AD. ApoE genotyping was performed by using standard methods. Hippocampal volumes were significantly smaller in AD cases than in control subjects. Hippocampal volumes did not differ significantly within either clinical group on the basis of ApoE genotype. Both the epsilon4 allele of ApoE and hippocampal atrophy were significantly but independently associated with AD.

Figure 1. Relationships between hippocampal volume, clinical group, and APOE genotype

This four panel collage illustrates a selected imaging slice through the body of the hippocampi in four different subjects. All four were women. The top left panel is a 79-year-old ∈4+ AD patient with normalized hippocampal volumes of 2.26. Top right is a 77-year-old e4− AD patient with normalized hippocampal volumes of 2.42. Bottom left is an 80-year-old ∈4+ control with normalized hippocampal volumes of 4.23. Bottom right is an 80-year-old ∈4− control with normalized hippocampal volumes of 4.36. The right hippocampus is traced as it would be for quantitation in each subject. The figure illustrates significant hippocampal atrophy in AD subjects compared to controls, but no difference in hippocampal volume between ∈4+ and ∈4− members of either clinical group. The hippocampal volumes are normalized by dividing the sum of the right plus left hippocampal volume in mm³ by total intracranial volume in cm³.