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

唐氏综合症中阿尔茨海默病炎症治疗的精准医学

• 批准号: 10296249
• 负责人: Michael S Rafii
• 金额: $ 232.88万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10296249
• 关键词: Adult; Age; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer’s disease biomarker; Amyloid beta-42; Amyloid beta-Protein; Animal Model; Anti-Inflammatory Agents; Antiinflammatory Effect; Antioxidants; Astrocytes; Attention; Basic Science; Biological; Biological Assay; Biological Markers; Classification; Clinical; Clinical Trials; Cohort Studies; Consultations; Data; Databases; Dementia; Development; Disease; Disease Progression; Down Syndrome; Enrollment; Epidemiology; Exhibits; Future; Genetic; Human; Immune signaling; Impaired cognition; Individual; Inflammation; Inflammatory; Infrastructure; Intellectual functioning disability; Intervention; Letters; Literature; Longitudinal Studies; Methods; Modeling; Nerve Degeneration; Neurons; Outcome; Pathologic; Patients; Persons; Phase III Clinical Trials; Plasma; Population; Predisposition; Prevention; Procedures; Property; Proteomics; Sampling; Subgroup; Symptoms; Techniques; Testing; Therapeutic; Therapeutic Trials; Time; Vitamin E; Work; aged; base; biobank; blood-based biomarker; cognitive performance; design; effective therapy; endophenotype; exosome; neuroinflammation; neuropathology; novel therapeutics; patient subsets; pre-clinical; precision medicine; predictive marker; prevent; tau Proteins; therapy outcome; treatment response; virtual

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

项目概要/摘要 唐氏综合症（DS）是智力障碍最常见的遗传原因，几乎所有唐氏综合症患者 60 岁时患有 AD。尽管过去 20 年我们对 DS 的理解以及如何 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） 目前还没有任何方法可以在临床上影响疾病的进展。 DS-AD 与散发的 AD 群体一样具有异质性，并且可以识别 DS-AD 的特定子集 特定的治疗将产生有意义的治疗反应，我们建议测试经过验证的生物标志物。 散发性 AD，我们建立的促炎症内表型分析将允许进行。 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，我们将利用之前生物库中的样本。 已完成 3 期临床试验“唐氏综合症老年人的维生素 E (NCT00056329)”。 拟议的工作，我们将在天然血浆和外泌体亚群上采用高通量蛋白质组学来 验证新技术并开发一个框架来设计更好的 DS-AD 治疗试验