Precision Medicine for Inflammatory Treatment for Alzheimer's Disease in Down Syndrome

项目摘要/摘要 唐氏综合症(DS)是导致智力残疾的最常见的遗传原因，几乎所有的DS患者都有 在60岁之前患上老年痴呆症。尽管在过去的20年里，我们对DS以及如何理解DS取得了令人兴奋的进步 遗传决定了AD的易感性，但在DS人群中治疗AD的临床试验很少(DS-AD) 目前还没有办法在临床上影响疾病的进展。我们假设人类的生物构成 DS-AD与零星AD群体一样具有异质性，并且识别DS-AD的特定子集 特定的治疗将产生有意义的治疗反应。我们建议测试一种经过验证的生物标记物 散发性阿尔茨海默病，我们已建立的促炎内表型分析。这一分析将允许 了解DS-AD患者之间免疫信号的差异以及这可能如何影响抗- 炎症对AD生物标志物的影响。在这项研究中，我们将利用以前的生物库样本 完成第三阶段临床试验，“维生素E在患有唐氏综合症的老年人中的应用(NCT00056329)”。为我们的 我们将在天然血浆和外切体亚群上应用高通量蛋白质组学 验证新技术并开发框架以设计更好的DS-AD治疗试验

PROJECT SUMMARY/ABSTRACT Down syndrome (DS) is the most common genetic cause of intellectual disability, with virtually all DS individuals having AD by age 60. Despite exciting advances over the past 20 years in our understanding of DS and how genetics confer susceptibility for AD, there have been few clinical trials to treat AD in the DS population (DS-AD) and currently no means to clinically impact disease progression. We hypothesize that the biological makeup of DS-AD is as heterogeneous as the sporadic AD population and that identifying specific subsets of DS-AD for particular treatments will yield meaningful therapeutic responses. We propose to test a validated biomarker for sporadic AD, our established proinflammatory endophenotype analysis. This analysis will allow for an understanding of differences in immune signaling between DS-AD individuals and how this may impact anti- inflammatory effects on AD biomarkers. For this study we will leverage biobanked samples from the previously completed Phase 3 clinical trial, “Vitamin E in Aged Persons with Down Syndrome (NCT00056329).” For our proposed work we will employ high throughput proteomics on native plasma and exosome subpopulations to validate new techniques and develop a framework for designing better therapeutic trials for DS-AD