A model for studying Alzheimer's Aβ42-induced toxicity in Drosophila melanogaster

Alyce Finelli, Anju Kelkar, Ho Juhn Song, Haidi Yang, Mary Konsolaki

Research output: Contribution to journalArticlepeer-review

204 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)365-375
Number of pages11
JournalMolecular and Cellular Neuroscience
Volume26
Issue number3
DOIs
StatePublished - Jul 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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