Alzheimer's disease in people with Down's syndrome: the prospects for and the challenges of developing preventative treatments
Alzheimer's disease in people with Down's syndrome: the prospects for and the challenges of developing preventative treatments
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DOI：
10.1007/s00415-016-8308-8
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发表时间：
2017-04-01
影响因子：
6
通讯作者：
Holland, Anthony
中科院分区：
文献类型：
--
作者：
Castro, Paula;Zaman, Shahid;Holland, Anthony
患有唐氏综合症（DS）的人在相对年轻的时候患阿尔茨海默病（AD）的风险很高。在智力残疾患者中未观察到这种增加的风险，原因除了DS之外，因此不太可能是由于神经发育障碍的非特异性影响，而是DS遗传学（21三体）的直接后果。鉴于淀粉样前体蛋白（APP）基因位于21号染色体上，淀粉样级联假说是解释这种风险的主要理论，其他遗传和环境因素改变了发病年龄和病程。目前正在研究几种靶向淀粉样蛋白通路并旨在改变AD病程的潜在疗法，这些疗法也可能用于治疗DS中的AD。然而，考虑到与AD相关的神经病理学在痴呆症表现之前许多年就开始了，任何预防性治疗都必须在症状发作之前就开始。为了能够进行此类干预试验，正在研究血浆、CSF、脑和视网膜生物标志物作为AD的替代早期诊断和结局指标。在这篇系统性综述中，我们考虑了DS人群中AD潜在预防性治疗的发展前景及其评价。
People with Down's syndrome (DS) are at high risk for developing Alzheimer's disease (AD) at a relatively young age. This increased risk is not observed in people with intellectual disabilities for reasons other than DS and for this reason it is unlikely to be due to non-specific effects of having a neurodevelopmental disorder but, instead, a direct consequence of the genetics of DS (trisomy 21). Given the location of the amyloid precursor protein (APP) gene on chromosome 21, the amyloid cascade hypothesis is the dominant theory accounting for this risk, with other genetic and environmental factors modifying the age of onset and the course of the disease. Several potential therapies targeting the amyloid pathway and aiming to modify the course of AD are currently being investigated, which may also be useful for treating AD in DS. However, given that the neuropathology associated with AD starts many years before dementia manifests, any preventative treatment must start well before the onset of symptoms. To enable trials of such interventions, plasma, CSF, brain, and retinal biomarkers are being studied as proxy early diagnostic and outcome measures for AD. In this systematic review, we consider the prospects for the development of potential preventative treatments of AD in the DS population and their evaluation.