A Multi-Cohort Study of ApoE ɛ4 and Amyloid-β Effects on the Hippocampus in Alzheimer’s Disease
Year: 2017
Type: article
Abstract: The apolipoprotein E (APOE) gene has been consistently shown to modulate the risk of Alzheimer's disease (AD). Here, using an AD and normal aging dataset primarily consisting of three AD multi-center studies (n = 1,781), we compared the effect of APOE and amyloid-β (Aβ) on baseline hippocampal volumes in AD patients, mild cognitive impairment (MCI) subjects, and healthy controls. A large sample of healthy adolescents (n = 1,387) was also used to compared hippocampal volumes between APOE groups. Subjects had undergone a magnetic resonance imaging (MRI) scan and APOE genotyping. Hippocampal volumes were processed using FreeSurfer. In the AD and normal aging dataset, hippocampal comparisons were performed in each APOE group and in ɛ4 carriers with positron emission tomography Aβ who were dichotomized (Aβ+/Aβ-) using previous cut-offs. We found a linear reduction in hippocampal volumes with ɛ4 carriers possessing the smallest volumes, ɛ3 carriers possessing intermediate volumes, and ɛ2 carriers possessing the largest volumes. Moreover, AD and MCI ɛ4 carriers possessed the smallest hippocampal volumes and control ɛ2 carriers possessed the largest hippocampal volumes. Subjects with both APOE ɛ4 and Aβ+ had the lowest hippocampal volumes when compared to Aβ- ɛ4 carriers, suggesting a synergistic relationship between APOE ɛ4 and Aβ. However, we found no hippocampal volume differences between APOE groups in healthy 14-year-old adolescents. Our findings suggest that the strongest neuroanatomic effect of APOE ɛ4 on the hippocampus is observed in AD and groups most at risk of developing the disease, whereas hippocampi of old and young healthy individuals remain unaffected.
Source: Journal of Alzheimer s Disease
DOI: 10.3233/jad-161097
Authors: Wasim Khan, Alzheimer–s Disease Neuroimaging Initiative, Vincent Giampietro, Tobias Banaschewski, Gareth J. Barker, Arun L.W. Bokde, Christian Büchel, Patricia Conrod, Herta Flor, Vincent Frouin, Hugh Garavan, Penny Gowland, Anreas Heinz, Bernd Ittermann, Hervé Lemaître, Frauke Nees, Tomas Paus, Zdenka Pausova, Marcella Rietschel, Michael N. Smolka, Andreas Ströhle, Jeurgen Gallinat, Bruno Vellas, Hilkka Soininen, Iwona Kloszewska, Magda Tsolaki, Patrizia Mecocci, Christian Spenger, Victor L. Villemagne, Colin L. Masters, J-Sebastian Muehlboeck, Lars Bäckman, Laura Fratiglioni, Grégoria Kalpouzos, Lars-Olof Wahlund, Gunther Schumann, Simon Lovestone, Steven C.R. Williams, Eric Westman, Andrew Simmons
Institutions: King's College London, Heidelberg University, Central Institute of Mental Health, Trinity College Dublin, University Medical Center Hamburg-Eppendorf, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, University of Vermont, University of Nottingham, Stiftung Charité, Charité – Universitätsmedizin Berlin, Physikalisch-Technische Bundesanstalt, Inserm, Assistance Publique – Hôpitaux de Paris, Université Paris Descartes, University of Toronto, Rotman Research Institute, McGill University, Hospital for Sick Children, Neuroimaging Center, Technische Universität Dresden, Université de Toulouse, University of Eastern Finland, Kuopio University Hospital, Medical University of Lodz, Aristotle University of Thessaloniki, University of Perugia, Karolinska Institutet, The University of Melbourne, Florey Institute of Neuroscience and Mental Health, Stockholm University
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: Alzheimer's Association, Alzheimer's Disease Neuroimaging Initiative, Stichting af Jochnick Foundation, Stiftelsen för Gamla Tjänarinnor, National Institute for Health and Care Research, Parkinson's UK, King's College London, European Commission, Commonwealth Scientific and Industrial Research Organisation, Forskningsrådet för Arbetsliv och Socialvetenskap, Vetenskapsrådet, Swedish Brain Power, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, Medical Research Council
OpenAlex ID: W2584381673