APOE2 Is Associated with Spatial Navigational Strategies and Increased Gray Matter in the Hippocampus

The Apolipoprotein E (APOE) gene has a strong association with Alzheimer's disease (AD). The epsilon 4 allele is a well-documented genetic risk factor of AD. In contrast, the epsilon 2 allele of the APOE gene is known to be protective against AD. Much of the focus on the APOE gene has been on the epsilon 4 allele in both young and older adults and few studies have looked into the cognitive and brain structure correlates of the epsilon 2 allele, especially in young adults. In the current study, we investigated the relationship between APOE genotype, navigation behavior, and hippocampal gray matter in healthy young adults. One-hundred and twenty-four healthy young adults were genotyped and tested on the 4on8 virtual maze, a task that allows for the assessment of navigation strategy. The task assesses the spontaneous use of either a hippocampus-dependent spatial strategy or a caudate nucleus-dependent response strategy. Of the 124 participants, 37 underwent structural magnetic resonance imaging (MRI). We found that epsilon 2 carriers use a hippocampus-dependent spatial strategy to a greater extent than epsilon 3 homozygous individuals and epsilon 4 carriers. We also found that APOE epsilon 2 allele carriers have more gray matter in the hippocampus compared to epsilon 3 homozygous individuals and EA carriers. Our findings suggest that the protective effects of the epsilon 2 allele may, in part, be expressed through increased hippocampus gray matter and increased use of hippocampus-dependent spatial strategies. The current article demonstrates the relationship between brain structure, navigation behavior, and APOE genotypes in healthy young adults.