A Genetic Model System to Study Alzheimer's Disease

Alzheimer’s Disease is a degenerative disorder of the central nervous system which causes progressive memory and cognitive decline during mid to late adult life. This disease is currently the fourth leading cause of death and a major cause of disability amongst ageing adults in Western societies. Despite the prevalence and the huge emotional and financial burdens imposed by this disease, no effective therapy exists. Recently, mutations in two genes called presenilin 1 and 2, have been linked to the early onset form of Familial Alzheimer’s Disease. This discovery provides a unique opportunity to generate animal and cellular m in Alzheimer’s Disease. In this proposal, I will describe how the fruit fly, Drosophila melanogaster, can be used as a model system to study the function of both normal and mutated forms of presenilins during normal development and ageing. I will also describe experiments which will allow us to identify other genes which may interact with presenilin and could also be involved in Alzheimer’s Disease. These studies are important for two major reasons. First they will provide insight into the normal function of presenilins which are a highly conserved, novel family of proteins. Second, the analysis of mutated presenilins and genes which can interact with them will allow us to develop an animal model which will in turn provide insights into the mechanisms of Alzheimer’s Disease necessary for the development of rational therapeutic approaches.