Alzheimer’s disease (AD) is a leading cause of dementia in the aging population, affecting some 4.5 million Americans; a number projected to reach 16 million by mid-century. Recently, links between AD and diabetes (which affects some 15-21 million Americans) have been described in clinical studies while intriguing experimental research suggests a convergence of pathogenic mechanisms for both diseases. Investigating these potential common mechanisms of neurodegenerative disease may lead to new therapeutic strategies. We propose to study the effect of diabetes on the progression of AD in transgenic mice, with the working hypothesis that the combination of both diseases will hasten onset and increase severity of brain disorders. We will pay particular attention to the enzyme GSK3, which is part of the insulin signaling pathway and is also involved in producing the plaques and tangles that are the hallmark of AD pathology. We will then use this model of combined AD and diabetes to investigate whether drugs currently being developed for treating either AD or diabetic neuropathy can protect animals from brain disorders associated with combined AD and diabetes.