Apolipoprotein E-Mimetics Inhibit Neurodegeneration and Restore Cognitive Functions in a Transgenic Drosophila Model of Alzheimer's Disease

Background: Mutations of the amyloid precursor protein gene (APP) are found in familial forms of Alzheimer's disease (AD) and some lead to the elevated production of amyloid-beta-protein (A beta). While A beta has been implicated in the causation of AD, the exact role played by A beta and its APP precursor are still unclear. Principal Findings: In our study, Drosophila melanogaster transgenics were established as a model to analyze AD-like pathology caused by APP overexpression. We demonstrated that age related changes in the levels and pattern of synaptic proteins accompanied progressive neurodegeneration and impairment of cognitive functions in APP transgenic flies, but that these changes may be independent from the generation of A beta. Using novel peptide mimetics of Apolipoprotein-E, COG112 or COG133 proved to be neuroprotective and significantly improved the learning and memory of APP transgenic flies. Conclusions: The development of neurodegeneration and cognitive deficits was corrected by injections of COG112 or COG133, novel mimetics of apolipoprotein-E (apoE) with neuroprotective activities.