Alzheimer's disease in Down syndrome: An overlooked population for prevention trials.
Alzheimer's disease in Down syndrome: An overlooked population for prevention trials.
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DOI：
10.1016/j.trci.2018.10.006
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发表时间：
2018-01-01
期刊：
影响因子：
--
通讯作者：
Zetterberg, Henrik
中科院分区：
文献类型：
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作者：
Strydom, Andre;Coppus, Antonia;Zetterberg, Henrik
发现患有唐氏综合征（DS）的成人具有与患有散发性阿尔茨海默病（AD）的个体相同的神经病理学特征，这在21号染色体上的淀粉样前体蛋白基因的鉴定中发挥了关键作用，并导致淀粉样级联假说。患有DS的个体一生中患痴呆症的风险超过90%，并且DS现在被认为是AD的一种遗传形式，类似于罕见的常染色体显性病因。正如DS将焦点放在淀粉样前体蛋白突变上一样，它也可能告诉我们操纵淀粉样蛋白通路对AD治疗结果的影响。然而，具有讽刺意味的是，患有DS的个体通常被排除在AD试验之外。本综述将讨论DS中AD的一级和二级预防试验以及此类试验的潜在障碍和解决方案，并描述欧洲范围内的Horizon 21联盟建立DS-AD预防临床试验网络。
The discovery that adults with Down syndrome (DS) have neuropathological features identical to individuals with sporadic Alzheimer's disease (AD) played a key role in the identification of the amyloid precursor protein gene on chromosome 21 and resulted in the amyloid cascade hypothesis. Individuals with DS have a lifetime risk for dementia in excess of 90%, and DS is now acknowledged to be a genetic form of AD similar to rare autosomal-dominant causes. Just as DS put the spotlight on amyloid precursor protein mutations, it is also likely to inform us of the impact of manipulating the amyloid pathway on treatment outcomes in AD. Ironically, however, individuals with DS are usually excluded from AD trials. This review will discuss primary and secondary prevention trials for AD in DS and the potential barriers and solutions to such trials and describe the Europe-wide Horizon21 Consortium to establish a DS-AD prevention clinical trials network.