TRANSGENIC EXPRESSION OF TAU AND APP IN MODELS OF ALZHEIMER'S DISEASE

这个子项目是众多研究子项目之一

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. Our studies focused on interactions between tau protein and the amyloid precursor protein (APP) in producing Alzheimer's disease pathology in the rodent (rat) and nonhuman primate (Saimiri sciureus) brain, with particular emphasis on tau protein in primates. We have shown that the ubiquitin C promoter produces consistently superior expression compared to the cytomegalovirus and platelet-derived growth factor promoters in adult rats. These findings were used to support the use of ubiquitin as the promoter in a new transgenic rat model of Alzheimer's disease (publications, below). Transgene expression of both green fluorescent protein and tau protein is localized primarily in neuronal somata, axons, and proximal dendrites, and remains intense up to 18 months of age in rats. We have also shown that tau expression can be similarly increased in squirrel monkeys. Finally, we recently completed dual fluorescence and immuno-electron microscopic evaluations of tau expression in rats. Our results show that enduring, focal expression of lentivirus-delivered transgenes is feasible in adult animals, presenting a unique opportunity to efficiently model AD pathogenesis in biologically advantageous species.