A commonly used Drosophila model of Alzheimer's disease generates an aberrant species of amyloid-β with an additional N-terminal glutamine residue

FEBS Lett. 2014 Oct 16;588(20):3739-43. doi: 10.1016/j.febslet.2014.08.022. Epub 2014 Aug 27.

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.

Keywords: Alzheimer’s disease; Amyloid; Drosophila; Neurodegeneration; Signal peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Amino Acid Sequence
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Drosophila / genetics
  • Drosophila / metabolism*
  • Drosophila / physiology
  • Glutamine / chemistry
  • Molecular Sequence Data
  • Peptide Fragments / chemistry*
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Phenotype*
  • Protein Sorting Signals
  • Protein Structure, Tertiary

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • Protein Sorting Signals
  • amyloid beta-protein (1-42)
  • Glutamine