Regional Atrophy of Transcallosal Prefrontal Connections in Cognitively Normal APOE ε4 Carriers

Purpose: To investigate the possible effect of the APOE epsilon 4 allele on age-related regional volume loss within the corpus callosum (CC) in healthy epsilon 4 allele carriers compared with noncarriers. Materials and Methods: A total of 211 subjects, ages 27 to 83 years, 51 epsilon 4 carriers and 160 noncarriers underwent T1-weighted MRI scan. All subjects had normal MRI scan and performed within normal range on a neuropsychological battery of tests. CC was segmented into seven functionally relevant regions using a previously published probabilistic map of the CC connectivity. We measured the volumes of the CC and its subregions. We used a regression model (with volumes as dependent and age as independent variables) and compared the slopes between carriers and noncarriers using an analysis of covariance model. We also carried out voxel-based-morphometry analysis to investigate the possible effect of the APOE epsilon 4 gene on the gray matter. Results: We found that the volume of the CC and all subregions decreased with increasing age in both groups. The slope was steeper in the APOE epsilon 4 carriers compared with-the noncarriers particularly in the prefrontal region (P = 0.02). No gray matter differences were observed between the two groups. Conclusion: APOE epsilon(4) polymorphism is associated with accelerated age-related volume loss in the prefrontal callosal tracts without gray matter loss. This result suggests the role of APOE epsilon(4) in the brain aging by primarily affecting white matter structures particularly in the frontal lobe.