Neurotoxic effects induced by the Drosophila amyloid-β peptide suggest a conserved toxic function

Katia Carmine-Simmen, Thomas Proctor, Jakob Tschäpe, Burkhard Poeck, Tilman Triphan, Roland Strauss, Doris Kretzschmar

Research output: Contribution to journalArticlepeer-review

94 Scopus citations


The accumulation of amyloid-β (Aβ) into plaques is a hallmark feature of Alzheimer's disease (AD). While amyloid precursor protein (APP)-related proteins are found in most organisms, only Aβ fragments from human APP have been shown to induce amyloid deposits and progressive neurodegeneration. Therefore, it was suggested that neurotoxic effects are a specific property of human Aβ. Here we show that Aβ fragments derived from the Drosophila orthologue APPL aggregate into intracellular fibrils, amyloid deposits, and cause age-dependent behavioral deficits and neurodegeneration. We also show that APPL can be cleaved by a novel fly β-secretase-like enzyme. This suggests that Aβ-induced neurotoxicity is a conserved function of APP proteins whereby the lack of conservation in the primary sequence indicates that secondary structural aspects determine their pathogenesis. In addition, we found that the behavioral phenotypes precede extracellular amyloid deposit formation, supporting results that intracellular Aβ plays a key role in AD.

Original languageEnglish (US)
Pages (from-to)274-281
Number of pages8
JournalNeurobiology of Disease
Issue number2
StatePublished - Feb 2009


  • APP
  • APPL
  • Amyloid
  • Behavioral deficits
  • Drosophila
  • Neurodegeneration
  • β-secretase

ASJC Scopus subject areas

  • Neurology


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