Effect of APOE epsilon 4 Allele on Cortical Thicknesses and Volumes: The AddNeuroMed Study

The apolipoprotein E (APOE) epsilon 4 allele is a risk factor for Alzheimer's disease (AD), but its effect on brain volumes is controversial. We explored the effect of the epsilon 4 allele on regional cortical thickness and volume measurements using an automated pipeline in 111 subjects with mild cognitive impairment (MCI), 115 AD patients, and 107 age-matched healthy controls. The clinical data were used as covariates in the thickness and volume comparisons. The epsilon 4 carriers had significantly smaller volume than non-carriers in caudate (p = 0.028) in controls; in amygdala and caudate in the MCI group (p <= 0.049); and in hippocampus and amygdala in the AD group (p <= 0.001). In the female subjects, the epsilon 4 carriers had significantly thinner cortical thickness or smaller volume than non-carriers in medial orbitofrontal gyrus and caudate in controls (p <= 0.014); in amygdala in MCI subjects (p = 0.047) and in hippocampus and amygdala in AD patients (p <= 0.024). However, in the male subjects, there were significant differences in cortical thickness and volume between epsilon 4 carriers and non-carriers in several structures in the MCI group, but no differences in the controls and AD patients. Compared to the non-carriers, the homozygous epsilon 4 carriers showed significant volume loss in hippocampus, deep nuclei, and caudal anterior cingulate cortex in MCI. In the AD group, the homozygous epsilon 4 carriers had significant volume loss in hippocampus and amygdala. We conclude that the APOE epsilon 4 allele modulates regional cortical thickness and volume in relation to diagnostic group and gender. The epsilon 4 allele has a dose-dependent and regionally specific effect on brain structures.