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: 8172384
• 负责人: ANTHONY WING SANG CHAN
• 金额: $ 5.48万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172384
• 关键词: Adverse effects; Age; Alzheimer' s Disease; Alzheimer' s disease model; Amyloid; Amyloid beta-Protein Precursor; Behavior; Blood; Brain; Cell Line; Cell model; Cognitive; Collection; Computer Retrieval of Information on Scientific Projects Database; Disease; ES Cell Line; Encephalitis; Funding; Genes; Genome; Grant; Human; Immunization; In Vitro; Institution; Longitudinal Studies; Macaca mulatta; Magnetic Resonance Imaging; Monkeys; Mus; Neurons; Proteins; Proteome; Reporting; Research; Research Personnel; Resources; Senile Plaques; Source; Stem cells; Transgenic Mice; Transgenic Organisms; United States National Institutes of Health; behavior test; cell type; improved; mouse model; nonhuman primate; tau Proteins

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Alzheimer's disease is a uniquely human disorder of old age that slowly destroys brain function. Recent research has shown that the disease is associated with a buildup of specific proteins in the brain; one of these proteins is amyloid-¿ (A¿), a fragment of the amyloid-precursor protein (APP) that forms senile plaques, and the other is the protein tau, which accumulates excessively in nerve cells. Transgenic mouse models have been created to study these proteins, but no mouse model fully resembles human Alzheimer's disease. For example, A¿-immunization therapy is remarkably successful in reducing A¿ and improving behavior in mice, but in humans with Alzheimer's disease, the same treatment resulted in brain inflammation and shrinkage that were not evident in mouse models. These serious side-effects have impeded the application of this promising treatment to humans. During the reporting period, we generated two transgenic AD monkeys. We are currently performing longitudinal studies including cognitive behavioral testing, MRI, routine blood collection for metabolite, genome and proteome profiling study. In addition, we have established rhesus embryonic stem cell lines that express both APPswe/ind and human tau genes. These stem cell lines are pluripotent and capable of differentiating into neuronal cell types in vitro. Ongoing effort is to further characterize such stem cell lines and develop them as a cell model for AD research.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以出现在其他 CRISP 条目中 列出的机构是。 中心，不一定是研究者的机构。 阿尔茨海默病是一种人类特有的老年疾病，它会慢慢破坏大脑功能。最近的研究表明，这种疾病与大脑中特定蛋白质的积累有关，其中一种蛋白质就是淀粉样蛋白。 (A¿) 是形成老年斑的淀粉样前体蛋白 (APP) 的片段，另一个是 tau 蛋白，它在神经细胞中过度积累，已经创建了转基因小鼠模型来研究这些蛋白质，但没有小鼠。模型与人类阿尔茨海默病完全相似，例如，A¿ -免疫疗法在很大程度上成功地减少了 A¿并改善了小鼠的行为，但在患有阿尔茨海默病的人类中，相同的治疗导致了大脑炎症和萎缩，而这在小鼠模型中并不明显，这些严重的副作用阻碍了这种有希望的治疗在人类中的应用。 在报告期内，我们培育了两只转基因AD猴，目前正在进行纵向研究，包括认知行为测试、MRI、代谢物常规血液采集、基因组和蛋白质组分析研究。此外，我们还建立了表达的恒河猴胚胎干细胞系。 APPswe/ind 和人类 tau 基因均具有多能性，并且能够在体外分化为神经细胞类型，目前正在努力进一步表征此类干细胞系并将其开发为神经细胞。 AD 研究的细胞模型。