title: 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.
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.
authors.affiliation: King's College London, Institute of Psychiatry, London, UK.|NIHR Biomedical Research Centre for Mental Health, King's College London, London, UK.|NIHR Biomedical Research Unit for Dementia, King's College London, London, UK.
authors.forename: Flavio
authors.initials: F
authors.lastname: Dell'Acqua
authors.affiliation: King's College London, Institute of Psychiatry, London, UK.|NIHR Biomedical Research Centre for Mental Health, King's College London, London, UK.|NIHR Biomedical Research Unit for Dementia, King's College London, London, UK.
authors.forename: Wasim
authors.initials: W
authors.lastname: Khan
authors.affiliation: King's College London, Institute of Psychiatry, London, UK.|NIHR Biomedical Research Centre for Mental Health, King's College London, London, UK.|NIHR Biomedical Research Unit for Dementia, King's College London, London, UK.
authors.forename: Natalie
authors.initials: N
authors.lastname: Gottlieb
authors.affiliation: King's College London, Institute of Psychiatry, London, UK.
authors.forename: Vincent
authors.initials: V
authors.lastname: Giampietro
authors.affiliation: King's College London, Institute of Psychiatry, London, UK.|NIHR Biomedical Research Centre for Mental Health, King's College London, London, UK.
authors.forename: Cedric
authors.initials: C
authors.lastname: Ginestet
authors.affiliation: King's College London, Institute of Psychiatry, London, UK.|NIHR Biomedical Research Centre for Mental Health, King's College London, London, UK.|NIHR Biomedical Research Unit for Dementia, King's College London, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Bouls
authors.affiliation: King's College London, Institute of Psychiatry, London, UK.|NIHR Biomedical Research Centre for Mental Health, King's College London, London, UK.|NIHR Biomedical Research Unit for Dementia, King's College London, London, UK.
authors.forename: Steven
authors.initials: S
authors.lastname: Newhouse
authors.affiliation: King's College London, Institute of Psychiatry, London, UK.|NIHR Biomedical Research Centre for Mental Health, King's College London, London, UK.|NIHR Biomedical Research Unit for Dementia, King's College London, London, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Dobson
authors.affiliation: Central Institute of Mental Health, Mannheim, Germany.|Medical Faculty Mannheim, University of Heidelberg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.affiliation: King's College London, Institute of Psychiatry, London, UK.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Barker
authors.affiliation: Institute of Neuroscience and Discipline of Psychiatry, School of Medicine, Trinity College Dublin, Dublin, Ireland.
authors.forename: Arun L W
authors.initials: AL
authors.lastname: Bokde
authors.affiliation: Universitaetsklinikum Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Büchel
authors.affiliation: King's College London, Institute of Psychiatry, London, UK.|Department of Psychiatry, Universite de Montreal, CHU Ste Justine Hospital, Canada.
authors.forename: Patricia
authors.initials: P
authors.lastname: Conrod
authors.affiliation: Central Institute of Mental Health, Mannheim, Germany.|Medical Faculty Mannheim, University of Heidelberg, Germany.
authors.forename: Herta
authors.initials: H
authors.lastname: Flor
authors.affiliation: Neurospin, Commissariat à l'Energie Atomique et aux Energies Alternatives, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Frouin
authors.affiliation: Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.|Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA.
authors.forename: Hugh
authors.initials: H
authors.lastname: Garavan
authors.affiliation: School of Physics and Astronomy, University of Nottingham, Nottingham, UK.
authors.forename: Penny
authors.initials: P
authors.lastname: Gowland
authors.affiliation: Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Anreas
authors.initials: A
authors.lastname: Heinz
authors.affiliation: 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.
authors.forename: Hervé
authors.initials: H
authors.lastname: Lemaítre
authors.affiliation: Central Institute of Mental Health, Mannheim, Germany.|Medical Faculty Mannheim, University of Heidelberg, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Nees
authors.affiliation: Rotman Research Institute, University of Toronto, Toronto, Canada.|School of Psychology, University of Nottingham, Nottingham, UK.|Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Tomas
authors.initials: T
authors.lastname: Paus
authors.affiliation: The Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Pausova
authors.affiliation: Central Institute of Mental Health, Mannheim, Germany.|Medical Faculty Mannheim, University of Heidelberg, Germany.
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.affiliation: Neuroimaging Center, Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Germany.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Smolka
authors.affiliation: Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ströhle
authors.affiliation: Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Jean
authors.initials: J
authors.lastname: Gallinat
authors.affiliation: Karolinska Institute, Stockholm, Sweden.
authors.forename: Eric
authors.initials: E
authors.lastname: Westman
authors.affiliation: King's College London, Institute of Psychiatry, London, UK.|NIHR Biomedical Research Centre for Mental Health, King's College London, London, UK.
authors.forename: Gunther
authors.initials: G
authors.lastname: Schumann
authors.affiliation: King's College London, Institute of Psychiatry, London, UK.|NIHR Biomedical Research Centre for Mental Health, King's College London, London, UK.|NIHR Biomedical Research Unit for Dementia, King's College London, London, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.affiliation: King's College London, Institute of Psychiatry, London, UK.|NIHR Biomedical Research Centre for Mental Health, King's College London, London, UK.|NIHR Biomedical Research Unit for Dementia, King's College London, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Simmons
mesh_terms: D000293:Adolescent; D000544:Alzheimer Disease / Q000235:genetics; D053329:Apolipoprotein E2 / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000033:anatomy & histology*; D015331:Cohort Studies; D003627:Data Interpretation, Statistical; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005060:Europe; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D066127:White Matter / Q000033:anatomy & histology*
chemical_list: D053329:Apolipoprotein E2; D053327:Apolipoprotein E4
keywords: Apolipoprotein E; diffusion tensor imaging; magnetic resonance imaging; tract based spatial statistics; young healthy adolescents