Tracking Axonal Transport of Mitochondria with GFP- Tagged Cytochrome-c Oxidase in a Drosophila Alzheimer’s Disease Model

The presence of Aß is correlated to activation of several possible downstream cascade mechanisms that can lead to neurodegeneration. Evidence shows that one possible down stream effect of Aß toxicity is the hyperphosphorylation of the microtubule stabilizing protein tau. In the hyperphosphorylated state, tau is inactive, thus microtubule structural integrity may be compromised. Microtubules are an essential component of axonal mitochondrial transport, both retrograde and anterograde. Due to substantial evidence that mitochondria create reactive oxygen species (ROS) when they are compromised, it is imperative to consider mitochondria as a source of oxidative stress in AD, particularly because toxicity of Aß has been tightly linked to oxidative stress in its molecular environment. Drosophila is a powerful model organism for studying AD pathology. Transgenic Drosophila, expressing human APP and one of its cleavage enzymes, BACE, produce Aß, yielding an AD-like pathology that is now a standard for AD research. Here, we propose to observe and quantify mitochondrial axonal transport both retrograde and anterograde in mitochondria in which cytochrome-c is tagged with GFP, in both the transgenic Drosophila model and in wild type flies. This comparison will allow us to determine whether axonal transport is compromised in AD pathology, elucidating a potential pathway of neurodegeneration in AD.