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

Article type: Research Article

Authors: Dell’Acqua, Flavio^{a; b; c; 1} | Khan, Wasim^{a; b; c; 1} | Gottlieb, Natalie^{a; b; c} | Giampietro, Vincent^a | Ginestet, Cedric^{a; b} | Bouls, David^{a; b; c} | Newhouse, Steven^{a; b; c} | Dobson, Richard^{a; b; c} | Banaschewski, Tobias^{d; e} | Barker, Gareth J.^a | Bokde, Arun L.W.ⁱ | Büchel, Christian^f | Conrod, Patricia^{a; g} | Flor, Herta^{d; e} | Frouin, Vincentⁿ | Garavan, Hugh^{q; r} | Gowland, Penny^s | Heinz, Anreas^h | Lemaítre, Hervé^j | Nees, Frauke^{d; e} | Paus, Tomas^{k; l; m} | Pausova, Zdenka^p | Rietschel, Marcella^{d; e} | Smolka, Michael N.^o | Ströhle, Andreas^h | Gallinat, Jean^h | Westman, Eric^t | Schumann, Gunther^{a; b} | Lovestone, Simon^{a; b; c} | Simmons, Andrew^{a; b; c; *} | the IMAGEN consortium ()

Affiliations: [a] King’s College London, Institute of Psychiatry, London, UK | [b] NIHR Biomedical Research Centre for Mental Health, King’s College London, London, UK | [c] NIHR Biomedical Research Unit for Dementia, King’s College London, London, UK | [d] Central Institute of Mental Health, Mannheim, Germany | [e] Medical Faculty Mannheim, University of Heidelberg, Germany | [f] Universitaetsklinikum Hamburg Eppendorf, Hamburg, Germany | [g] Department of Psychiatry, Universite de Montreal, CHU Ste Justine Hospital, Canada | [h] Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité – Universitätsmedizin Berlin, Germany | [i] Institute of Neuroscience and Discipline of Psychiatry, School of Medicine, Trinity College Dublin, Dublin, Ireland | [j] 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 | [k] Rotman Research Institute, University of Toronto, Toronto, Canada | [l] School of Psychology, University of Nottingham, Nottingham, UK | [m] Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada | [n] Neurospin, Commissariat à l’Energie Atomique et aux Energies Alternatives, Paris, France | [o] Neuroimaging Center, Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Germany | [p] The Hospital for Sick Children, University of Toronto, Toronto, Canada | [q] Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland | [r] Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA | [s] School of Physics and Astronomy, University of Nottingham, Nottingham, UK | [t] Karolinska Institute, Stockholm, Sweden

Correspondence: [*] Correspondence to: Dr. Andrew Simmons, Department of Neuroimaging, Institute of Psychiatry, King’s College London, De Crespigny Park, London SE5 8AF, UK. Tel.: +44 20 3228 3055; Fax: +44 20 3228 2116; [email protected]

Note: [1] These authors contributed equally to this work.

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.

Keywords: Apolipoprotein E, diffusion tensor imaging, magnetic resonance imaging, tract based spatial statistics, young healthy adolescents

DOI: 10.3233/JAD-140519

Journal: Journal of Alzheimer's Disease, vol. 47, no. 4, pp. 977-984, 2015