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.
JAD. 2015-08-11; 47(4): 977-984
DOI: 10.3233/jad-140519
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1. J Alzheimers Dis. 2015;47(4):977-84. doi: 10.3233/JAD-140519.
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.
Dell’Acqua F(1)(2)(3), Khan W(1)(2)(3), Gottlieb N(1)(2)(3), Giampietro V(1),
Ginestet C(1)(2), Bouls D(1)(2)(3), Newhouse S(1)(2)(3), Dobson R(1)(2)(3),
Banaschewski T(4)(5), Barker GJ(1), Bokde AL(6), Büchel C(7), Conrod P(1)(8),
Flor H(4)(5), Frouin V(9), Garavan H(10)(11), Gowland P(12), Heinz A(13),
Lemaítre H(14), Nees F(4)(5), Paus T(15)(16)(17), Pausova Z(18), Rietschel
M(4)(5), Smolka MN(19), Ströhle A(13), Gallinat J(13), Westman E(20), Schumann
G(1)(2), Lovestone S(1)(2)(3), Simmons A(1)(2)(3); IMAGEN consortium
(http://www.imagen-europe.com).
Author information:
(1)King’s College London, Institute of Psychiatry, London, UK.
(2)NIHR Biomedical Research Centre for Mental Health, King’s College London,
London, UK.
(3)NIHR Biomedical Research Unit for Dementia, King’s College London, London, UK.
(4)Central Institute of Mental Health, Mannheim, Germany.
(5)Medical Faculty Mannheim, University of Heidelberg, Germany.
(6)Institute of Neuroscience and Discipline of Psychiatry, School of Medicine,
Trinity College Dublin, Dublin, Ireland.
(7)Universitaetsklinikum Hamburg Eppendorf, Hamburg, Germany.
(8)Department of Psychiatry, Universite de Montreal, CHU Ste Justine Hospital,
Canada.
(9)Neurospin, Commissariat à l’Energie Atomique et aux Energies Alternatives,
Paris, France.
(10)Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
(11)Departments of Psychiatry and Psychology, University of Vermont, Burlington,
VT, USA.
(12)School of Physics and Astronomy, University of Nottingham, Nottingham, UK.
(13)Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité –
Universitätsmedizin Berlin, Germany.
(14)Institut National de la Santé et de la Recherche Médicale, INSERM CEA Unit
1000 « Imaging & Psychiatry », University Paris Sud, Orsay, and AP-HP Department of
Adolescent Psychopathology and Medicine, Maison de Solenn, University Paris
Descartes, Paris, France.
(15)Rotman Research Institute, University of Toronto, Toronto, Canada.
(16)School of Psychology, University of Nottingham, Nottingham, UK.
(17)Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
(18)The Hospital for Sick Children, University of Toronto, Toronto, Canada.
(19)Neuroimaging Center, Department of Psychiatry and Psychotherapy, Technische
Universität Dresden, Germany.
(20)Karolinska Institute, Stockholm, Sweden.
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.
DOI: 10.3233/JAD-140519
PMID: 26401776 [Indexed for MEDLINE]