TY - JOUR
T1 - Gene-environment interaction research and transgenic mouse models of Alzheimer's disease
AU - Rutten, B. P.F.
AU - Chouliaras, L.
AU - Sierksma, A. S.R.
AU - Kenis, G.
AU - Prickaerts, J.
AU - Lemmens, M. A.M.
AU - Brasnjevic, I.
AU - Van Donkelaar, E. L.
AU - Martinez-Martinez, P.
AU - Losen, M.
AU - De Baets, M. H.
AU - Kholod, N.
AU - Van Leeuwen, F.
AU - Hof, P. R.
AU - Van Os, J.
AU - Steinbusch, H. W.M.
AU - Van Den Hove, D. L.A.
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=78349273286&partnerID=8YFLogxK
U2 - 10.4061/2010/859101
DO - 10.4061/2010/859101
M3 - Review article
AN - SCOPUS:78349273286
SN - 2090-8024
JO - International Journal of Alzheimer's Disease
JF - International Journal of Alzheimer's Disease
M1 - 859101
ER -