Age-Dependent Neurodegeneration and Alzheimer-Amyloid Plaque Formation in Transgenic Drosophila

Isabell Greeve, Doris Kretzschmar, Jakob Andreas Tschäpe, Anika Beyn, Claire Brellinger, Michaela Schweizer, Roger M. Nitsch, Rita Reifegerste

Research output: Contribution to journalReview articlepeer-review

202 Scopus citations

Abstract

β-Amyloid peptides that are cleaved from the amyloid precursor protein (APP) play a critical role in Alzheimer's disease (AD) pathophysiology. Here, we show that in Drosophila, the targeted expression of the key genes of AD, APP, the β-site APP-cleaving enzyme BACE, and the presenilins led to the generation of β-amyloid plaques and age-dependent neurodegeneration as well as to semilethality, a shortened life span, and defects in wing vein development. Genetic manipulations or pharmacological treatments with secretase inhibitors influenced the activity of the APP-processing proteases and modulated the severity of the phenotypes. This invertebrate model of amyloid plaque pathology demonstrates Aβ-induced neurodegeneration as a basic biological principle and may allow additional genetic analyses of the underlying molecular pathways.

Original languageEnglish (US)
Pages (from-to)3899-3906
Number of pages8
JournalJournal of Neuroscience
Volume24
Issue number16
DOIs
StatePublished - Apr 21 2004

Keywords

  • Aging
  • Alzheimer
  • Degeneration
  • Dementia
  • Drosophila
  • Neuropathology

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Age-Dependent Neurodegeneration and Alzheimer-Amyloid Plaque Formation in Transgenic Drosophila'. Together they form a unique fingerprint.

Cite this