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Neurosci."],"abstract":"<jats:p>There are an estimated 6 million people with Down syndrome (DS) worldwide. In developed countries, the vast majority of these individuals will develop Alzheimer's disease neuropathology characterized by the accumulation of amyloid-\u03b2 (A\u03b2) plaques and tau neurofibrillary tangles within the brain, which leads to the early onset of dementia (AD-DS) and reduced life-expectancy. The mean age of onset of clinical dementia is ~55 years and by the age of 80, approaching 100% of individuals with DS will have a dementia diagnosis. DS is caused by trisomy of chromosome 21 (Hsa21) thus an additional copy of a gene(s) on the chromosome must cause the development of AD neuropathology and dementia. Indeed, triplication of the gene <jats:italic>APP<\/jats:italic> which encodes the amyloid precursor protein is sufficient and necessary for early onset AD (EOAD), both in people who have and do not have DS. However, triplication of other genes on Hsa21 leads to profound differences in neurodevelopment resulting in intellectual disability, elevated incidence of epilepsy and perturbations to the immune system. This different biology may impact on how AD neuropathology and dementia develops in people who have DS. Indeed, genes on Hsa21 other than <jats:italic>APP<\/jats:italic> when in three-copies can modulate AD-pathogenesis in mouse preclinical models. Understanding this biology better is critical to inform drug selection for AD prevention and therapy trials for people who have DS. Here we will review rodent preclinical models of AD-DS and how these can be used for both <jats:italic>in vivo<\/jats:italic> and <jats:italic>ex vivo<\/jats:italic> (cultured cells and organotypic slice cultures) studies to understand the mechanisms that contribute to the early development of AD in people who have DS and test the utility of treatments to prevent or delay the development of disease.<\/jats:p>","DOI":"10.3389\/fnins.2022.909669","type":"journal-article","created":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T05:20:10Z","timestamp":1654579210000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Rodent Modeling of Alzheimer's Disease in Down Syndrome: In vivo and ex vivo Approaches"],"prefix":"10.3389","volume":"16","author":[{"given":"Cl\u00edona","family":"Farrell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige","family":"Mumford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances K.","family":"Wiseman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.neurobiolaging.2017.05.002","article-title":"Age exacerbates abnormal protein expression in a mouse model of Down syndrome","volume":"57","author":"Ahmed","year":"2017","journal-title":"Neurobiol. 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