Development and Validation of an Aged Adult onset Alzheimer's Disease model in Drosophila melanogaster. Siddhita D Mhatre, Sarah Michelson, Janine Gomes, Daniel Marenda. Department of Biology, Drexel University, Philadelphia, PA.
Late-onset Alzheimers disease (LOAD) is a progressive neurodegenerative disorder that involves the accumulation of -amyloid (A) plaques and neurofibrillary tangles in the brains of elderly patients. Those that are afflicted often experience symptoms including memory loss, confusion, and behavioral changes. In an attempt to analyze this disorder, we developed a novel Aged AD model using Drosophila melanogaster. Through the Gal4-UAS system, we are able to express low levels of human AD genes - amyloid precursor protein (APP) and -site APP cleaving enzyme (BACE) - specifically in the flys nervous system. Advantages of our model include the onset of behavioral and neuropathological symptoms later in the fly's lifespan due to gradual accrual of A within the central nervous system (CNS) adding age as the key factor in this model. Our model provides us with a comparable timeline for the disease pathology of LOAD in humans, and it will be an excellent instrument for the rapid testing of small molecules for therapeutic intervention in vivo.