Dissecting Alzheimer disease in Down syndrome using mouse models.
Dissecting Alzheimer disease in Down syndrome using mouse models.
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DOI：
10.3389/fnbeh.2015.00268
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发表时间：
2015
影响因子：
3
通讯作者：
Fisher EM
中科院分区：
文献类型：
--
作者：
Choong XY;Tosh JL;Pulford LJ;Fisher EM
唐氏综合症（DS）是一种常见的遗传性疾病，由21号染色体的三个拷贝（21三体）引起。这大大增加了阿尔茨海默病（AD）的风险，但尽管几乎所有DS患者在40岁时都有AD神经病理学，但并非所有人都发展为痴呆症。为了剖析21三体对DS表型（包括与AD相关的表型）的遗传贡献，已经产生了一系列DS小鼠模型，其对于与人21号染色体同线的染色体区段是三体的。在这里，我们考虑了人类AD在DS（AD-DS）中的关键特征，以及我们目前对AD和DS小鼠模型中相关表型的了解。我们继续审查未来AD-DS模型所需的重要特征，以了解这种类型的痴呆症，并强调与所有AD风险人群相关的致病机制。
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.