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

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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.