title: Transgenic mouse models of Alzheimer's disease.
abstract: Alzheimer's disease is the most common cause of senile dementia in the United States and Europe. At present, there is no effective treatment. Given the disease's prevalence and poor prognosis, the development of animal models has been a high research priority. Transgenic modeling has been pursued on the basis of the amyloid hypothesis and has taken advantage of mutations in the amyloid precursor protein and the presenilins that cause familial forms of Alzheimer's disease. Modeling has been most aggressively pursued in mice, for which the techniques of genetic modification are well developed. Transgenic mouse models now exist that mimic a range of Alzheimer's disease-related pathologies. Although none of the models fully replicates the human disease, the models have contributed significant insights into the pathophysiology of beta-amyloid toxicity, particularly with respect to the effects of different beta-amyloid species and the possible pathogenic role of beta-amyloid oligomers. They have also been widely used in the preclinical testing of potential therapeutic modalities and have played a pivotal role in the development of immunotherapies for Alzheimer's disease that are currently in clinical trials. These models will, without a doubt, continue to play central roles in preclinical testing and be used as tools for developing insights into the biological basis of Alzheimer's disease.
authors.affiliation: Neurology Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, NY, USA. gregory.elder@mssm.edu
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Elder
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gama Sosa
authors.forename: Rita
authors.initials: R
authors.lastname: De Gasperi
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D053763:Presenilins / Q000235:genetics / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D053763:Presenilins