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

项目总结/摘要 唐氏综合症（DS）是智力残疾的最常见遗传原因，几乎所有DS个体 在60岁之前患有AD。尽管在过去的20年里，我们对DS的理解和如何理解有了令人兴奋的进步， 遗传学赋予AD易感性，但在DS人群中治疗AD的临床试验很少（DS-AD） 并且目前没有临床上影响疾病进展的手段。我们假设， DS-AD与散发性AD人群一样是异质性的， 特定的治疗将产生有意义的治疗反应。我们建议测试一种有效的生物标志物， 散发性AD，我们建立的促炎性内表型分析。这一分析将使 了解DS-AD个体之间免疫信号的差异以及这如何影响抗- 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3期临床试验，“维生素E在唐氏综合症老年人（NCT 00056329）。”为我们 我们将在天然血浆和外来体亚群上采用高通量蛋白质组学， 验证新技术，并为设计更好的DS-AD治疗试验制定框架

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