Grant: Operating Grant

Alzheimer's disease (AD) is the most common form of dementia. It is an incurable, degenerative and terminal disease that afflicts an estimated 27 million people worldwide. In the brain, it is characterized by the presence of two protein aggregates: amyloid plaques, and neurofibrillary tangles (NFTs). NFTs are composed of bundles of aggregated tau protein. There is clinical evidence that diabetes is associated with an increased risk of AD, but there is very little understanding of the mechanism by which diabetes could affect AD. The overall goal of this project is therefore to clarify the impacts that diabetes has on tau protein pathogenesis, one of the pathological hallmarks of Alzheimer's disease. My hypothesis is that diabetes will induce tau pathology by deregulating signaling cascades in the brain. In turn, this will result in tau dysfunction and memory impairment. To address my hypothesis, I will develop the three following specific aims: Aim 1: To characterize the effect diabetes on tau pathogenesis in vivo Aim 2: To elucidate the mechanisms of tau pathogenesis in diabetes in vivo Aim 3: To investigate the functional and behavioral effects of tau pathology during diabetes The aims focus on one aspect of Alzheimer's disease: tau pathogenesis. Completion of those aims will help clarify the impact of diabetes on Alzheimer's disease pathology. In turn, this understanding will help the development of treatments or life-style strategies destined to check the advance of the disease. In light of the increased incidence of diabetes in the young population that predict higher incidence of senile dementias in the coming years, our study may provide invaluable information for the treatment and prevention of sporadic AD.