White Matter Alterations in Cognitively Normal apoE ε2 Carriers: Insight into Alzheimer Resistance?

BACKGROUND AND PURPOSE: The basis for decreased vulnerability to AD among apoE epsilon 2 carriers is unknown. The purpose of this study was to use diffusion tensor imaging to detect possible differences in white matter integrity between. cognitively normal elderly apoE epsilon 2 carriers and apoE epsilon 3/epsilon 3 controls. MATERIALS AND METHODS: Thirty-nine cognitively normal elderly individuals (19 heterozygous carriers of the apoE epsilon 2 allele, 20 apoE epsilon 3/epsilon 3 subjects as controls) underwent diffusion tensor MR imaging on a 4T scanner. Fractional anisotropy, MD, and axial and radial diffusivity were compared using a ROI approach. In addition, an exploratory whole-brain analysis of fractional anisotropy between the 2 groups was undertaken using TBSS. RESULTS: apoE epsilon 2 carriers had higher FA in the posterior cingulate white matter (P = .01) and anterior corpus callosum (P = .005) than apoE epsilon 3/epsilon 3 controls, secondary to lower radial diffusivity. No significant differences in the FA of the posterior corpus callosum, anterior cingulate white matter, or parahippocampal white matter were seen. Whole-brain TBSS analysis detected regions of higher FA in the apoE epsilon 2 group in the superior longitudinal fasciculus, right thalamus, and the bilateral anterior limbs of the internal capsule, in addition to the posterior cingulum and corpus callosum (P < .005). There were no regions in which the apoE epsilon 3/epsilon 3 group had higher FA. CONCLUSIONS: apoE epsilon 2 carriers harbor more robust white matter integrity that may be associated with decreased vulnerability to developing AD. This provides further evidence that regional DTI metrics may serve as early imaging biomarkers of AD risk.