Dissecting Alzheimer disease in Down syndrome using mouse models

• Published in: Frontiers in behavioral neuroscience Vol. 9; p. 268
• Main Authors: Choong, Xun Yu, Tosh, Justin L, Pulford, Laura J, Fisher, Elizabeth M C
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 13.10.2015; Frontiers Media S.A
• Subjects: Age; Aging; Alzheimer Disease; Alzheimer's disease; Animal models; APP; Chromosome 21; Chromosomes; Dementia; Dementia disorders; Down Syndrome; Down's syndrome; Genes; Hypotheses; Metabolism; Mortality; mouse models; Mutation; Neurodegenerative diseases; Neuroscience; Pathogenesis; Pathology; Phenotypes; Population; Proteins; Proteomics; Rodents; Synteny; Trisomy; trisomy 21; United Kingdom > UK; mouse models; APP; Down syndrome; Alzheimer disease; trisomy 21
• ISSN: 1662-5153; 1662-5153
• DOI: 10.3389/fnbeh.2015.00268

Down syndrome (DS) is a common genetic condition caused by the presence of three copies of chromosome 21 (trisomy 21). This greatly increases the risk of Alzheimer disease (AD), but although virtually all people with DS have AD neuropathology by 40 years of age, not all develop dementia. To dissect the genetic contribution of trisomy 21 to DS phenotypes including those relevant to AD, a range of DS mouse models has been generated which are trisomic for chromosome segments syntenic to human chromosome 21. Here, we consider key characteristics of human AD in DS (AD-DS), and our current state of knowledge on related phenotypes in AD and DS mouse models. We go on to review important features needed in future models of AD-DS, to understand this type of dementia and so highlight pathogenic mechanisms relevant to all populations at risk of AD.