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Disrupted white matter structural networks in healthy older adult APOE ε4 carriers – An international multicenter DTI study

Cavedo, E; Lista, S; Rojkova, K; Chiesa, PA; Houot, M; Brueggen, K; Blautzik, J; ... Hampel, H; + view all (2017) Disrupted white matter structural networks in healthy older adult APOE ε4 carriers – An international multicenter DTI study. Neuroscience , 357 pp. 119-133. 10.1016/j.neuroscience.2017.05.048. Green open access

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Abstract

The 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.

Type: Article
Title: Disrupted white matter structural networks in healthy older adult APOE ε4 carriers – An international multicenter DTI study
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neuroscience.2017.05.048
Publisher version: https://doi.org/10.1016/j.neuroscience.2017.05.048
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, Diffusion Tensor Imaging, Apolipoprotein E, Multicenter Study, White Matter Integrity, Aging, Mild Cognitive Impairment, Apolipoprotein-E Genotype, Positron-Emission-Tomography, Corpus-Callosum Atrophy, Voxel-Based Morphometry, Alzheimers-Disease, Diffusion-Tensor, Human Brain, Spatial Statistics, Amyloid-Beta
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation
URI: https://discovery.ucl.ac.uk/id/eprint/10049132
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