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Cavedo, Enrica; Lista, Simone; Rojkova, Katrine; Chiesa, Patrizia A.; Houot, Marion; Brüggen, Katharina; Blautzik, Janusch; Bokde, Arun L. W.; Dubois, Bruno; Barkhof, Frederik; Pouwels, Petra J. W.; Teipel, Stefan; Hampel, Harald (2017): Disrupted White Matter Structural Networks in Healthy Older Adult APOE Epsilon 4 Carriers - An International Multicenter DTI Study. In: Neuroscience, Vol. 357: pp. 119-133
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The epsilon 4 allelic variant of the Apolipoprotein E gene (APOE epsilon 4) is the best-established genetic risk factor for late-onset Alzheimer's disease (AD). White matter (WM) microstructural damages measured with Diffusion Tensor Imaging (DTI) represent an early sign of fiber tract disconnection in AD. We examined the impact of APOE epsilon 4 on WM microstructure in elderly individuals from the multicenter European DTI Study on Dementia. Voxelwise statistical analysis of fractional anisotropy (FA), mean diffusivity, radial and axial diffusivity (MD, radD and axD respectively) was carried out using Tract-Based Spatial Statistics. Seventy-four healthy elderly individuals - 31 APOE epsilon 4 carriers (APOE epsilon 4+) and 43 APOE epsilon 4 non-carriers (APOE epsilon 4-) -were considered for data analysis. All the results were corrected for scanner acquisition protocols, age, gender and for multiple comparisons. APOE e4+ and APOE epsilon 4- subjects were comparable regarding sociodemographic features and global cognition. A significant reduction of FA and increased radD was found in the APOE epsilon 4+ compared to the APOE epsilon 4- in the cingulum, in the corpus callosum, in the inferior fronto-occipital and in the inferior longitudinal fasciculi, internal and external capsule. APOE epsilon 4+, compared to APOE epsilon 4- showed higher MD in the genu, right internal capsule, superior longitudinal fasciculus and corona radiate. Comparisons stratified by center supported the results obtained on the whole sample. These findings support previous evidence in monocentric studies indicating a modulatory role of APOE epsilon 4 allele on WM microstructure in elderly individuals at risk for AD suggesting early vulnerability and/or reduced resilience of WM tracts involved in AD. (C) 2017 IBRO.