title: A model for studying Alzheimer's Abeta42-induced toxicity in Drosophila melanogaster.
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 Abeta peptides is widely considered a causative event in the disease, the mechanisms by which Abeta peptides cause neurodegeneration and the processes of Abeta clearance and degradation remain unclear. To address these issues, we have expressed the Abeta peptides in Drosophila melanogaster. We show that overexpression of Abeta42 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 Abeta42 phenotypes by lowering the levels of the Abeta42 peptide, supporting the role of neprilysin in the catabolism of Abeta peptides in vivo. We propose that our Drosophila model is suitable for the study and elucidation of Abeta metabolism and toxicity at the genetic level.
authors.affiliation: Department of Functional Genomics, Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
authors.forename: Alyce
authors.initials: A
authors.lastname: Finelli
authors.forename: Anju
authors.initials: A
authors.lastname: Kelkar
authors.forename: Ho-Juhn
authors.initials: HJ
authors.lastname: Song
authors.forename: Haidi
authors.initials: H
authors.lastname: Yang
authors.forename: Mary
authors.initials: M
authors.lastname: Konsolaki
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics* / Q000633:toxicity; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics*; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000235:genetics*; D006801:Humans; D015260:Neprilysin / Q000502:physiology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics* / Q000633:toxicity; D010641:Phenotype
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D015260:Neprilysin