title: A commonly used Drosophila model of Alzheimer's disease generates an aberrant species of amyloid-β with an additional N-terminal glutamine residue.
abstract: Expression of human amyloid-β (Aβ) in Drosophila is frequently used to investigate its toxicity in vivo. We expressed Aβ1-42 in the fly using a secretion signal derived from the Drosophila necrotic gene, as described in several previous publications. Surface-enhanced laser desorption/ionization TOF MS analysis revealed that the Aβ produced contained an additional glutamine residue at the N-terminus. AβQ+1-42 was found to have increased protein abundance and to cause more severe neurodegenerative effects than wild type Aβ1-42 as assessed by locomotor activity and lifespan assays. These data reveal that a commonly used model of Alzheimer's disease generates incorrect Aβ peptide.
authors.affiliation: Department of Genetics, University of Melbourne, Australia.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Allan
authors.affiliation: Florey Department of Neuroscience and Mental Health, The University of Melbourne, Australia.
authors.forename: Keyla A
authors.initials: KA
authors.lastname: Perez
authors.affiliation: Bio21 Institute, The University of Melbourne, Australia.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Barnham
authors.affiliation: Florey Department of Neuroscience and Mental Health, The University of Melbourne, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Camakaris
authors.affiliation: School of Biological Sciences, Monash University, Australia. Electronic address: richard.burke@monash.edu.
authors.forename: Richard
authors.initials: R
authors.lastname: Burke
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004330:Drosophila / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005973:Glutamine / Q000737:chemistry; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D021382:Protein Sorting Signals; C075222:amyloid beta-protein (1-42); D005973:Glutamine
keywords: Alzheimer’s disease; Amyloid; Drosophila; Neurodegeneration; Signal peptide