DEVELOPING A NON-HUMAN PRIMATE MODEL OF ALZHEIMER DISEASE

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 我们已经成功地建立了第一个阿尔茨海默病的转基因灵长类动物模型。我们目前有两个健康的雌性，生殖系淀粉样前体蛋白转基因恒河猴，年龄41（RQd 12; AD-1）和31（RNn 12; AD-2）个月，和一个31个月大的雄性猴子（ROn 12; AD-3）嵌合整合的转基因。这些动物现在正接近繁殖年龄，该项目的下一个关键阶段是增加转基因动物的数量，确认转基因的种系传递性，并保持基线行为，细胞和神经生物学分析，以捕捉这种独特模型的新兴转基因相关表型。 的大小，行为的复杂性和生物接近人类的转基因AD猴的理想的纵向研究的早期生物标志物和行为变化，成像研究与磁共振和选择性放射性配体，代谢分析蛋白质周转，神经病理演变通过脑活检，和测试的实验治疗方法，如干细胞或基因治疗。

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.