Justine Anne A. Guevarra¹ and Fernando Vonhoff¹

Alzheimer’s Disease (AD) is the most common form of dementia and is associated with mutations in certain genes including APP. The human APP gene encodes for amyloid precursor protein (App), which is a transmembrane protein expressed in several tissues and organs, including the brain. Although its physiological functions remain elusive, studies in mice and fruit flies show that lack of App proteins results in developmental and locomotor deficits, which can be rescued by the expression of the human App, confirming its conserved properties. App is also a metalloprotein, which can bind to metals such as copper and zinc. Interestingly, recent studies display increasing evidence on the possible link between metals and neurodegenerative disorders. Post-mortem AD brains reveal accumulation of metals such as aluminum, copper, zinc, etc. To our knowledge, there is no known study investigating the possible protective role of the fly ortholog, appl, on metal exposure in flies. This project aims to investigate the effects of metal exposure in flight behavior in Drosophila melanogaster. Current observations showed a decline in flight performance in appl null flies compared to wild-type flies following aluminum treatment, suggesting a protective role for appl. Surprisingly, copper treatment did not influence the appl null flies but resulted in lower survival rate and flight performance in wild-type flies. Overall, the knowledge gained from the experiments will serve as a reference for future studies in mammals and broaden the understanding of the mechanisms involving App / Appl and metal toxicity in flies.

¹Department of Biological Sciences, University of Maryland, Baltimore County, USA