Accelerated age-related cortical thinning in healthy carriers of apolipoprotein E ɛ4

Effects of APOE genotype on age-related slopes of cortical thinning was estimated by measuring the thickness of the cerebral cortex on a point-by-point basis across the cortical mantle in 96 healthy non-demented volunteers aged 48–75 years. Fifty nine were APOE ɛ4− (no ɛ4 allele) and 37 were ɛ4+ (1 or 2 ɛ4 alleles). The genotype groups had similar age, sex and IQ. Two T1-weighted MP-RAGE sequences were averaged for each participant to yield images with high signal-to-noise ratio, and quantified using semi-automated analysis tools. ɛ4 carriers had thicker cortex than non-carriers in several frontal and temporal areas in both hemispheres, but showed a steeper age-related decline in adjacent areas. Upon comparison of the ɛ4-specific age-related thinning with previously published patterns of thinning in normal aging and Alzheimer's disease (AD), we conclude that APOE ɛ4 may function to accelerate thinning in areas found to decline in aging (medial prefrontal and pericentral cortex), but also to initiate thinning in areas associated with AD and amyloid-β aggregation (occipitotemporal and basal temporal cortex).