Presence of ApoE epsilon 4 Allele Associated with Thinner Frontal Cortex in Middle Age

The presence of an ApoE epsilon 4 allele (epsilon 4+) increases the risk of developing Alzheimer's disease (AD). Previous studies support an adverse relationship between epsilon 4+ status and brain structure and function in mild cognitive impairment and AD; in contrast, the presence of an epsilon 2 allele may be protective. Whether these findings reflect disease-related effects or pre-existing endophenotypes, however, remains unclear. The present study examined the influence of ApoE allele status on brain structure solely during middle-age in a large, national sample. Participants were 482 men, ages 51-59, from the Vietnam Era Twin Study of Aging (VETSA). T1-weighted images were used in volumetric segmentation and cortical surface reconstruction methods to measure regional volume and thickness. Primary linear mixed effects models predicted structural measures with ApoE status (epsilon 3/3, epsilon 2/3, epsilon 3/4) and control variables for effects of site, non-independence of twin data, age, and average cranial vault or cortical thickness. Relative to the epsilon 3/3 group, the epsilon 3/4 group demonstrated significantly thinner cortex in superior frontal and left rostral and right caudal midfrontal regions; there were no significant effects of epsilon 4 status on any temporal lobe measures.