Analysis of toxicity associated with Alzheimer's beta-amyloid. using Drosophila as a model system
My research interests focus on understanding Alzheimer's disease (AD), a neurological disorder resulting in the degeneration and eventual death of neurons in brain centers controlling memory, cognition and behavior. Human genetic analyses have resulted in the identification of a handful of genes responsible for genetically inherited forms of Alzheimer's disease but our understanding of basic mechanisms that lead to the more common sporadic forms of this disease is still limited.
Overproduction of beta-amyloid (Ab) peptides in the brain is widely believed to be a causative event in the disease process. Research work in my lab has concentrated on trying to better understand the molecular pathways associated with production as well as toxicity and clearance of Ab peptides, using Drosophila as a model system.
We have shown that flies expressing Ab peptides can closely mimic phenotypic, behavioral and physiological aspects of Alzheimer's disease. Ab peptides accumulate in a dose- and age dependent manner in flies, causing phenotypes that are associated with neurodegeneration, such as locomotion defects and shorter lifespan. We are currently using these flies in genetic screens to identify genes involved in Ab metabolism and toxicity, In order to understand the functions of such genes, a variety of approaches is used, including genetics as well as behavioral, molecular, biochemical and cell-biological methods.