Alzheimer's disease is a neurological disorder resulting in the degeneration and death of brain neurons controlling memory, cognition and behavior. Although overproduction of Aβ peptides is widely considered a causative event in the disease, the mechanisms by which Aβ peptides cause neurodegeneration and the processes of Aβ clearance and degradation remain unclear. To address these issues, we have expressed the Aβ peptides in Drosophila melanogaster. We show that overexpression of Aβ 42 peptides in the nervous system results in phenotypes associated with neuronal degeneration in a dose- and age-dependent manner. We further show that a mutation in a Drosophila neprilysin gene suppresses the Aβ 42 phenotypes by lowering the levels of the Aβ 42 peptide, supporting the role of neprilysin in the catabolism of Aβ peptides in vivo. We propose that our Drosophila model is suitable for the study and elucidation of Aβ metabolism and toxicity at the genetic level.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cellular and Molecular Neuroscience
- Cell Biology