LENTIVIRAL-MEDIATED EXPRESSION OF TRANSGENIC BETA-APP AND PRESENILIN IN MONKEYS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本项目的目的是利用慢病毒载体和疾病相关的转基因为建立新型阿尔茨海默病（AD）病理学转基因模型奠定基础。目前的AD转基因小鼠模型概括了该疾病的某些方面，但它们没有发展出人类特有的完整退行性表型。由于阿尔茨海默病的长期和进行性，重要的是转基因在细胞中长时间强烈表达。为此，我们已经表明，泛素启动子产生最好的神经元转基因表达，并且转基因蛋白在大鼠中保持强烈表达长达18个月。最近，我们已经证明，慢病毒表达人tau蛋白的转基因导致在神经元中，在短短3周内出现累积的tau蛋白。此外，与Yerkes成像中心的Timothy Duong博士合作，我们已经开始对松鼠猴进行磁共振成像研究，我们还开始测试Goodman和Votaw博士开发的新型化合物，用于在阿尔茨海默病样淀粉样病变的啮齿动物和灵长类动物模型中对老年斑和脑淀粉样血管病进行体内成像。

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. The goal of this project is to lay the foundation for creating novel transgenic models of Alzheimer 's disease (AD) pathology using a lentiviral vectors and disease-linked transgenes. Current transgenic mouse models of AD recapitulate some aspects of the disease, but they do not develop the full degenerative phenotype that is unique to humans. Because of the long-term and progressive nature of Alzheimer's disease, it is important for the transgene to strongly expressed by cells for a long period of time. To this end, we have shown that the ubiquitin promoter yields that best neuronal transgene expression, and that transgenic protein remains strongly expressed for as long as 18 months in rats. More recently, we have demonstrated that lentiviral expression of a transgene for human tau protein results in the appearance, in neurons, of accumulated tau proteins in as little as 3 weeks. In addition, in collaboration with Dr. Timothy Duong of the Yerkes Imaging Center, we have begun magnetic resonance imaging studies of squirrel monkeys and we have also begun testing novel compounds, developed by Drs. Goodman and Votaw, for imaging senile plaques and cerebral amyloid angiopathy in vivo in rodent and primate models of Alzheimer-like ¿-amyloid pathology.