DEVELOPING A NON-HUMAN PRIMATE MODEL OF ALZHEIMER DISEASE

开发阿尔茨海默病的非人类灵长类动物模型

• 批准号: 8357439
• 负责人: ANTHONY WING SANG CHAN
• 金额: $ 4.12万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357439
• 关键词: Age; Alzheimer' s disease model; Amyloid beta-Protein Precursor; Animals; Behavioral; Biological; Biological Markers; Biopsy; Brain; Breeding; Evolution; Female; Funding; Grant; Human; Image; Longitudinal Studies; Macaca mulatta; Magnetic Resonance; Metabolic; Modeling; Monkeys; National Center for Research Resources; Neurobiology; Phenotype; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Source; Staging; Stem cells; Testing; Therapeutic; Transgenes; Transgenic Animals; Transgenic Organisms; United States National Institutes of Health; aged; cost; gene therapy; male; nonhuman primate; protein degradation; radioligand

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We have succeeded in establishing the first transgenic primate models of Alzheimer's disease. We currently have two healthy female, germline amyloid precursor protein-transgenic rhesus monkeys, aged 41 (RQd12; AD-1) and 31 (RNn12; AD-2) months, and a 31-month-old male monkey (ROn12; AD-3) with mosaic integration of the transgene. These animals are now approaching breeding age, and the next critical stage of the project is to increase the number of transgenic animals, to confirm the germline transmissibility of the transgene, and to maintain baseline behavioral, cellular and neurobiological analyses in order to capture the emerging transgene-related phenotype of this unique model. The size, behavioral complexity and biological proximity to humans make the transgenic AD monkey ideal for the longitudinal study of early biomarkers and behavioral changes, imaging studies with magnetic resonance and selective radioligands, metabolic analysis of protein turnover, neuropathological evolution through brain biopsy, and testing of experimental therapeutic approaches such as stem cells or genetic therapy.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 我们成功建立了第一个阿尔茨海默病转基因灵长类动物模型。我们目前有两只健康的雌性种系淀粉样前体蛋白转基因恒河猴，年龄分别为 41 个月（RQd12；AD-1）和 31 个月（RNn12；AD-2），以及一只 31 个月大的雄性猴子（ROn12；AD- 3) 转基因的嵌合整合。这些动物现已接近繁殖年龄，该项目的下一个关键阶段是增加转基因动物的数量，确认转基因的种系遗传性，并维持基线行为、细胞和神经生物学分析，以捕获新兴的转基因动物。这种独特模型的转基因相关表型。 转基因 AD 猴的体型、行为复杂性和生物学上与人类的接近性使得转基因 AD 猴成为早期生物标志物和行为变化的纵向研究、磁共振和选择性放射性配体的成像研究、蛋白质周转的代谢分析、通过脑活检进行的神经病理学进化和测试的理想选择。干细胞或基因疗法等实验性治疗方法。