• Neuroscience · Aug 2017

    Multicenter Study

    Disrupted white matter structural networks in healthy older adults APOE ε4 carriers - An International Multicenter DTI Study.

    • Enrica Cavedo, Simone Lista, Katrine Rojkova, Patrizia A Chiesa, Marion Houot, Katharina Brueggen, Janusch Blautzik, Bokde Arun L W ALW Cognitive Systems Group, Discipline of Psychiatry, School of Medicine, Trinity College Dublin, Dublin, Ireland; and Trinity College Institute of Neuros, Bruno Dubois, Frederik Barkhof, Pouwels Petra J W PJW Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Centre, The Netherlands., Stefan Teipel, Harald Hampel, and Alzheimer Precision Medicine Initiative (APMI).
    • AXA Research Fund & UPMC Chair, Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Paris 06, Inserm, CNRS, Institut du Cerveau et de la Moelle Épinière (ICM), Département de Neurologie, Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Hôpital Pitié-Salpêtrière, Boulevard de l'hôpital, F-75013 Paris, France; Laboratory of Alzheimer's Neuroimaging and Epidemiology, IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy. Electronic address: enrica.cavedo@gmail.com.
    • Neuroscience. 2017 Aug 15; 357: 119-133.

    AbstractThe ε4 allelic variant of the Apolipoprotein E gene (APOE ε4) 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 ε4 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 ε4 carriers (APOE ε4+) and 43 APOE ε4 non-carriers (APOE ε4-) -were considered for data analysis. All the results were corrected for scanner acquisition protocols, age, gender and for multiple comparisons. APOE ε4+ and APOE ε4- subjects were comparable regarding sociodemographic features and global cognition. A significant reduction of FA and increased radD was found in the APOE ε4+ compared to the APOE ε4- in the cingulum, in the corpus callosum, in the inferior fronto-occipital and in the inferior longitudinal fasciculi, internal and external capsule. APOE ε4+, compared to APOE ε4- 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 ɛ4 allele on WM microstructure in elderly individuals at risk for AD suggesting early vulnerability and/or reduced resilience of WM tracts involved in AD.Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

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