Alzheimer’s in Drosophila Melanogaster: Testing a Model System
Authors:
Eddie Anton, Shelby Chun FatMentor:
Cathy McElwain, Associate Professor of Biology, Loyola Marymount UniversityThe extensive genetic tools available in Drosophila melanogaster make it an attractive system for studying human disease. The Alzheimer’s Disease has been modeled in D. melanogaster using two alternative, artificial genes that encode for the aggregating polypeptide (Aß42) and a non-aggregating control polypeptide (C99). In mammals, Alzheimer’s is correlated with the appearance of aggregating Aß42 polypeptide in the brain. Drosophila expressing this fragment have reduced activity and cognitive capability compared to the controls, mimicking certain effects of Alzheimer’s Disease. We are in the early stages of testing reduced learning and memory in Aß42 expressing flies. In standard protocols, flies are trained to avoid light using quinine as an adverse stimulus and later tested to see if they have learned the avoidance behavior. It has been previously demonstrated that control flies show a higher level of memory than do Aß42 flies. In an apparatus of our own design, neither the control nor experimental flies exhibited phototactic behavior. Of 80 flies initially tested, only 4 (3 controls and 1 experimental) entered the lighted chamber even after an extended testing period. We report on a series of experiments designed to potentiate the phototactic response. To date, none of these interventions has increased the percentage of flies entering the lighted chamber. Current efforts are focused on entraining the light cycle and changing the apparatus. Once we have established a repeatable difference in learning between Aß42 and C99, we will use the system to test the effects of a peptide that has been reported to interfere with aggregation in vitro by our collaborator, Dr. David Moffet. We anticipate that flies fed the interfering peptide will demonstrate increased learning compared to the untreated Aß42s.