Tract Based Spatial Statistic Reveals No Differences in White Matter Microstructural Organization between Carriers and Non-Carriers of the APOE ɛ4 and ɛ2 Alleles in Young Healthy Adolescents

  • Flavio Dell'Acqua
  • Wasim Khan
  • Natalie Gottlieb
  • Vincent Giampietro
  • Cedric Ginestet
  • David Bouls
  • Steven Newhouse
  • Richard Dobson
  • Tobias Banaschewski
  • Gareth J Barker
  • Arun L W Bokde
  • Christian Büchel
  • Patricia Conrod
  • Herta Flor
  • Vincent Frouin
  • Hugh Garavan
  • Penny Gowland
  • Anreas Heinz
  • Hervé Lemaítre
  • Frauke Nees
  • Tomas Paus
  • Zdenka Pausova
  • Marcella Rietschel
  • Michael N Smolka
  • Andreas Ströhle
  • Jean Gallinat
  • Eric Westman
  • Gunther Schumann
  • Simon Lovestone
  • Andrew Simmons

Abstract

The apolipoprotein E (APOE) ɛ4 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 WM tracts in carriers and non-carriers of the APOE ɛ4 and ɛ2 alleles using an unbiased whole brain analysis technique (Tract Based Spatial Statistics) in a healthy young adolescent (14 years) 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 = 1,300 s/mm2 and isotropic resolution of 2.4×2.4×2.4 mm). No significant differences in WM structure were found in diffusion indices between carriers and non-carriers of the APOE ɛ4 and ɛ2 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 ɛ4 and ɛ2 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.

Bibliografische Daten

OriginalspracheEnglisch
ISSN1387-2877
DOIs
StatusVeröffentlicht - 11.08.2015
PubMed 26401776