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

IU/JAX 阿尔茨海默病精密模型中心：代谢组学

• 批准号: 9537115
• 负责人: Gregory W Carter
• 金额: $ 17.65万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9537115
• 关键词: Academic Medical Centers; Alleles; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease model; Animal Disease Models; Animal Model; Animals; Area; Behavior; Biochemistry; Biological; Biological Markers; Biological Process; Biology; Blood Vessels; Cause of Death; Cessation of life; Clinic; Clinical; Clinical Trials; Clustered Regularly Interspaced Short Palindromic Repeats; Communities; Complex; Computer Simulation; Data; Data Set; Databases; Dementia; Development; Disease; Disease model; Drug Industry; Early Diagnosis; Effectiveness; Elderly; Ensure; Etiology; Failure; Functional disorder; Funding; Generations; Genes; Genetic; Genetic Models; Genome engineering; Genomic approach; Genomics; Goals; Growth; Heterogeneity; Human; Human Genetics; Image; Indiana; Informatics; Institution; International; Intervention; Laboratories; Late Onset Alzheimer Disease; Liquid substance; Mammalian Genetics; Medical; Medicine; Modeling; Mus; Nerve Degeneration; Outcome; Outcome Measure; Pharmacology; Phenotype; Preclinical Testing; Presenile Alzheimer Dementia; Prevalence; Process; Psychology; Research; Research Infrastructure; Resources; Sampling; Scientist; Systems Biology; Testing; The Jackson Laboratory; Therapeutic; Translations; United States; United States National Institutes of Health; Universities; Variant; amyloid precursor protein processing; animal imaging; cholesterol trafficking; clinically relevant; cost; data resource; disability; disease phenotype; drug testing; effective therapy; gene interaction; genetic technology; genome editing; genome sequencing; genome wide association study; human disease; imaging biomarker; innovation; insight; metabolomics; mouse genome; mouse model; multidisciplinary; neuroimaging; neuroinflammation; neuropathology; next generation; novel; novel therapeutics; pre-clinical; preclinical study; prevent; repository; symposium; synergism; web portal

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. !

项目概要 阿尔茨海默病（AD）是老年人痴呆、残疾和死亡的主要原因。尽管最近 虽然我们对AD的基本生物学机制的理解取得了进展，但我们还不知道如何 预防AD或获得批准的疾病改善干预。两者都是减缓或停止增长的关键 痴呆症的患病率。国家阿尔茨海默病项目法案（NAPA）旨在预防和有效治疗AD 到2025年，通过病因学、早期发现和治疗的创新研究。为了支持国家适应行动方案的目标， 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 Summit是下一代AD动物模型的开发，这将被证明在以下方面更具预测性 临床前研究，从而加快药物测试管道。虽然我们目前的AD动物模型 为AD疾病机制提供了多种新的见解，迄今为止，它们尚未被成功利用。 来预测已经进入AD临床试验的疗法的有效性。印第安纳州大学 (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IU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）和相当专业的临床前药物测试与JAX的八个 在哺乳动物遗传学和疾病建模方面拥有数十年的专业知识， 新的精确的阿尔茨海默病（AD）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、多学科的团队，包括遗传学家和遗传技术专家， 定量和计算生物学家，AD和神经成像临床专家，药理学家和 世界领先的精密动物疾病模型的发展，拥有集体 预测疾病建模需求的能力，因为它们出现在国际舞台上。这将允许 IU/JAX ADPMC有效和高效地为AD科学界服务。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经过验证的传播管道以及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 国际吧最终，这将加速动物模型的应用， 可能的医疗效益。IU/JAX ADPMC的具体目标是： 1.最大化人类数据集，以确定AD的假定变体，基因和生物标志物。 2.生成和表征下一代AD小鼠模型。 3.开发下一代AD小鼠模型并开发临床前测试管道。 !