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International Journal of Alzheimer’s Disease
Volume 2010, Article ID 859101, 27 pages
Review Article

Gene-Environment Interaction Research and Transgenic Mouse Models of Alzheimer's Disease

1School for Mental Health and Neuroscience (MHeNS), Faculty of Health, Medicine and Life Sciences, European Graduate School of Neuroscience (EURON), Maastricht University Medical Centre, P.O. Box 616, 6200 MD Maastricht, The Netherlands
2Department of Neuroscience, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA
3Division of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK
4Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, 97080 Würzburg, Germany

Received 29 May 2010; Accepted 31 July 2010

Academic Editor: A. I. Bush

Copyright © 2010 L. Chouliaras et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The etiology of the sporadic form of Alzheimer's disease (AD) remains largely unknown. Recent evidence has suggested that gene-environment interactions (GxE) may play a crucial role in its development and progression. Whereas various susceptibility loci have been identified, like the apolipoprotein E4 allele, these cannot fully explain the increasing prevalence of AD observed with aging. In addition to such genetic risk factors, various environmental factors have been proposed to alter the risk of developing AD as well as to affect the rate of cognitive decline in AD patients. Nevertheless, aside from the independent effects of genetic and environmental risk factors, their synergistic participation in increasing the risk of developing AD has been sparsely investigated, even though evidence points towards such a direction. Advances in the genetic manipulation of mice, modeling various aspects of the AD pathology, have provided an excellent tool to dissect the effects of genes, environment, and their interactions. In this paper we present several environmental factors implicated in the etiology of AD that have been tested in transgenic animal models of the disease. The focus lies on the concept of GxE and its importance in a multifactorial disease like AD. Additionally, possible mediating mechanisms and future challenges are discussed.