Longitudinal changes in medial temporal cortical thickness in normal subjects with the APOE-4 polymorphism

Abstract

People with the apolipoprotein-Eepsilon4 (APOE-4) genetic risk for Alzheimer's disease show morphologic differences in medial temporal lobe regions when compared to non-carriers of the allele. Using a high-resolution MRI and cortical unfolding approach, our aim was to determine the rate of cortical thinning among medial temporal lobe subregions over the course of 2 years. We hypothesized that APOE-4 genetic risk would contribute to longitudinal cortical thickness change in the subiculum and entorhinal cortex, regions preferentially susceptible to Alzheimer's disease related pathology. Thirty-two cognitively intact subjects, mean age 61 years, 16 APOE-4 carriers, 16 non-carriers, underwent baseline and follow-up MRI scans. Over this relatively brief interval, we found significantly greater cortical thinning in the subiculum and entorhinal cortex of APOE-4 carriers when compared to non-carriers of the allele. Average cortical thinning across all medial temporal lobe subregions combined was also significantly greater for APOE-4 carriers. This finding is consistent with the hypothesis that carrying the APOE-4 allele renders subjects at a higher risk for developing Alzheimer's disease.

Fig. 1

Cortical unfolding method. Using high-resolution magnetic resonance images (A), white matter (B, blue) and cerebrospinal fluid (B, yellow) are manually segmented. The resulting gray matter strip is then computationally unfolded and flattened. Boundaries (C) between subregions are delineated on the original images and then projected onto the flat map (D, right side shown). CADG=anterior CA fields and dentate gyrus, CA23DG=CA fields 2, 3 and dentate gyrus, CA1=CA field 1, SUB=subiculum, ERC=entorhinal cortex, PRC=perirhinal cortex, PHC=parahippocampal cortex, FUS=fusiform cortex.

Fig. 2

Cortical thickness change over time (%) across subregions. The color-coded flat maps visualize cortical thickness change over the 2-year follow-up period in APOE-4 carriers and non-carriers for both hemispheres separately. The graph below provides average (across both hemispheres) cortical thickness change for all subregions over time (mean±SE). Significant between-group differences are indicated (*, p<0.05, two-tailed). APOE-4 carriers compared to non-carriers showed significant greater cortical thinning in SUB, ERC, and Global. CADG=anterior CA fields and dentate gyrus, CA23DG=CA fields 2, 3 and dentate gyrus, CA1=CA field 1, SUB=subiculum, ERC=entorhinal cortex, PRC=perirhinal cortex, PHC=parahippocampal cortex, FUS=fusiform cortex, Global=average thickness across all subregions, e3=non-APOE-4 carriers, e4=APOE-4 subjects.