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 journalArticle

181 Citations (Scopus)

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

Fingerprint

Amyloid beta-Protein Precursor
Amyloid Plaques
Drosophila
Alzheimer Disease
Presenilins
Amyloid Precursor Protein Secretases
Invertebrates
Amyloid
Veins
Peptide Hydrolases
Pharmacology
Pathology
Phenotype
Gene Expression
Peptides
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Greeve, I., Kretzschmar, D., Tschäpe, J. A., Beyn, A., Brellinger, C., Schweizer, M., ... Reifegerste, R. (2004). Age-Dependent Neurodegeneration and Alzheimer-Amyloid Plaque Formation in Transgenic Drosophila. Journal of Neuroscience, 24(16), 3899-3906. https://doi.org/10.1523/JNEUROSCI.0283-04.2004

Age-Dependent Neurodegeneration and Alzheimer-Amyloid Plaque Formation in Transgenic Drosophila. / Greeve, Isabell; Kretzschmar, Doris; Tschäpe, Jakob Andreas; Beyn, Anika; Brellinger, Claire; Schweizer, Michaela; Nitsch, Roger M.; Reifegerste, Rita.

In: Journal of Neuroscience, Vol. 24, No. 16, 21.04.2004, p. 3899-3906.

Research output: Contribution to journalArticle

Greeve, I, Kretzschmar, D, Tschäpe, JA, Beyn, A, Brellinger, C, Schweizer, M, Nitsch, RM & Reifegerste, R 2004, 'Age-Dependent Neurodegeneration and Alzheimer-Amyloid Plaque Formation in Transgenic Drosophila', Journal of Neuroscience, vol. 24, no. 16, pp. 3899-3906. https://doi.org/10.1523/JNEUROSCI.0283-04.2004
Greeve, Isabell ; Kretzschmar, Doris ; Tschäpe, Jakob Andreas ; Beyn, Anika ; Brellinger, Claire ; Schweizer, Michaela ; Nitsch, Roger M. ; Reifegerste, Rita. / Age-Dependent Neurodegeneration and Alzheimer-Amyloid Plaque Formation in Transgenic Drosophila. In: Journal of Neuroscience. 2004 ; Vol. 24, No. 16. pp. 3899-3906.
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