The IU/JAX Alzheimer's Disease Precision Models Center: Aging

项目总结总体构成部分 阿尔茨海默病(AD)是导致老年人痴呆、残疾和死亡的主要原因。尽管最近 我们对阿尔茨海默病基本生物学机制的了解进展，我们还不知道如何 预防阿尔茨海默病或采取经批准的疾病修改干预措施。两者对减缓或阻止增长都是必不可少的 痴呆症患病率。《国家阿尔茨海默氏症项目法案》旨在预防和有效治疗阿尔茨海默病 到2025年，通过病因学、早期发现和治疗方面的创新研究。为了支持纳帕的目标， NIA赞助的2015年阿尔茨海默病研究确定的目标研究领域之一 顶峰是下一代AD动物模型的发展，它将被证明在 临床前研究，从而加快药物测试流水线。虽然我们目前的AD动物模型已经 提供了对AD疾病机制的多种新见解，到目前为止还没有被成功利用 以预测已进入AD临床试验的治疗方法的有效性。印第安纳大学 (IU)/杰克逊实验室(JAX)阿尔茨海默病精确模型中心(IU/JAX ADPMC)将 利用伊利诺伊大学在神经退行性研究方面的优势，包括作为NIA支持的25年 阿尔茨海默病中心(ADC)和JAX的八项临床前药物测试方面的丰富专业知识 几十年来在哺乳动物遗传学和疾病建模方面的专业知识，以开发、验证和传播 阿尔茨海默病(AD)的新的精确动物模型。此外，Iu/JAX ADMPC包含SAGE Bionetworks提供数据组织和传播方面的专业知识。Iu/JAX ADPMC带来了 一个国际化的多学科团队--包括遗传学家和基因技术专家， 定量和计算生物学家，AD和神经成像方面的临床专家，药理学家和 在疾病精确动物模型开发方面的世界领先者--拥有集体 当疾病模型需求出现在国际舞台上时，能够预见这些需求。这将允许 Iu/JAX ADPMC为AD科学界提供有效和高效的服务。Iu/JAX ADPMC将 生成新的AD建模流程和管道、数据资源、研究结果和模型 将通过JAX和Sage久经考验的传播管道以及NIA迅速共享- 支持AD中心、学术医疗中心、研究机构和制药行业 全世界。最终，这将加速动物模型的最大进步的应用 可能的医疗福利。IU/JAX ADPMC的具体目标是： 1.最大化人类数据集，以确定AD的假定变异、基因和生物标记物。 2.建立和鉴定下一代AD小鼠模型。 3.验证下一代阿尔茨海默病小鼠模型，开发临床前测试流水线。 好了！

PROJECT SUMMARY OVERALL COMPONENT Alzheimer's disease (AD) is a major cause of dementia, disability and death in the elderly. Despite recent advances in our understanding of basic biological mechanisms underlying AD, we do not yet know how to prevent AD or have an approved disease modifying intervention. Both are essential to slow or stop the growth in dementia prevalence. The National Alzheimer's Project Act (NAPA) seeks to prevent and effectively treat AD by 2025 through innovative research on etiology, early detection, and therapeutics. In support of NAPA's goals, one of the targeted areas of research identified at the NIA sponsored 2015 Alzheimer's Disease Research Summit was the development of the next generation of animal models of AD that will prove more predictive in preclinical studies and thus accelerate the drug testing pipeline. While our current animal models of AD have provided multiple novel insights into AD disease mechanisms, thus far they have not been successfully utilized to predict the effectiveness of therapies that have moved into AD clinical trials. The Indiana University (IU)/Jackson Laboratory (JAX) Alzheimer's Disease Precision Models Center (IU/JAX ADPMC) will leverage IU's strengths in neurodegenerative research including 25 years as an NIA-supported Alzheimer's Disease Center (ADC) and considerable expertise in preclinical drug testing with JAX's eight decades of expertise in mammalian genetics and disease modeling to develop, validate and disseminate new, precise animal models of Alzheimer's disease (AD). In addition, the IU/JAX ADMPC contains Sage Bionetworks to provide expertise in data organization and dissemination. The IU/JAX ADPMC brings together an international, multi-disciplinary team—including geneticists and genetics technology experts, quantitative and computational biologists, clinical experts in AD and neuroimaging, pharmacologists and world leaders in the development of precision animal models of disease—that possesses the collective ability to foresee disease modeling needs as they emerge on the international stage. This will allow the IU/JAX ADPMC to serve the AD scientific community effectively and efficiently. The IU/JAX ADPMC will generate new AD modeling processes and pipelines, data resources, research results and models that will be swiftly shared through JAX's and Sage's proven dissemination pipelines and through the NIA- supported AD Centers, academic medical centers, research institutions and the pharmaceutical industry worldwide. Ultimately, this will accelerate the application of advances in animal models for the greatest possible medical benefit. The Specific Aims of the IU/JAX ADPMC are: 1. Maximize Human Datasets to Identify Putative Variants, Genes and Biomarkers for AD. 2. Generate and Characterize the Next Generation of Mouse Models of AD. 3. Validate the Next Generation of Mouse Models of AD and Develop a Preclinical Testing Pipeline. !