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Tract Based Spatial Statistic reveals no differences in white matter microstructural organisation between carriers and non-carriers of the ApoE ε4 and ε2 alleles in young healthy adolescents

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Flavio Dell' Acqua ; Wasim Nawaz Khan ; Natalie Nicole Gottlieb ; Vincent Pierre Giampietro ; Cedric Emmanuel Ginestet ; David Tharwat Tawfik Bouls ; Steven Newhouse ; Richard Dobson ; Tobias Banaschewski ; Gareth John Barker ; Arun L W Bokde ; Christian Buechel ; Patricia Conrod ; Herta Flor ; Vincent Frouin ; Hugh Garavan ; Penny Gowland ; Anreas Heinz ; Herve Lemaître ; Frauke Nees ; Tomas Paus ; Zdenka Pausova ; Marcella Rietschel ; Michael N. Smolka ; Andreas Stroehle ; Jean Gallinat ; Eric Westrnan ; Gunther Schumann ; Simon Lovestone ; Andrew Simmons

Original languageEnglish
JournalJournal of Alzheimer's Disease
StateAccepted/In press - 2015

King's Authors

Abstract

The Apolipoprotein E (ApoE) ε4 allele is the best established genetic risk factor for Alzheimer’s disease (AD) and has been previously associated with alterations in structural gray matter and changes in functional brain activity in healthy middle-aged individuals and older non-demented subjects. In order to determine the neural mechanism by which ApoE polymorphisms affect white matter (WM) structure, we investigated the diffusion characteristics of white matter tracts in carriers and non-carriers of the ApoE ε4 and ε2 alleles using an unbiased whole brain analysis technique (Tract Based Spatial Statistics (TBSS)) in a healthy young adolescent (14years) cohort. A large sample of healthy young adolescents (n=575) were selected from the European neuroimaging-genetics IMAGEN study with available ApoE status and accompanying diffusion imaging data. MR Diffusion data was acquired on 3T systems using 32 diffusion-weighted (DW) directions and 4 non-DW volumes (b-value = 1300 s/mm2 and isotropic resolution of 2.4x2.4x2.4 mm). No significant differences in WM structure were found in diffusion indices between carriers and non-carriers of the ApoE ε4 and ε2 alleles, and dose-dependent effects of these variants were not established, suggesting that differences in WM structure are not modulated by the ApoE polymorphism. In conclusion, our results suggest that microstructural properties of WM structure are not associated with the ApoE ε4 and ε2 alleles in young adolescence, suggesting that the neural effects of these variants are not evident in 14-year olds and may only develop later in life.

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