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Age-dependent neurodegeneration and Alzheimer-amyloid plaque formation in transgenic Drosophila


Greeve, I; Kretzschmar, D; Tschäpe, J A; Beyn, A; Brellinger, C; Schweizer, M; Nitsch, R M; Reifegerste, R (2004). Age-dependent neurodegeneration and Alzheimer-amyloid plaque formation in transgenic Drosophila. Journal of Neuroscience, 24(16):3899-3906.

Abstract

Beta-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 beta-site APP-cleaving enzyme BACE, and the presenilins led to the generation of beta-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 Abeta-induced neurodegeneration as a basic biological principle and may allow additional genetic analyses of the underlying molecular pathways.

Abstract

Beta-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 beta-site APP-cleaving enzyme BACE, and the presenilins led to the generation of beta-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 Abeta-induced neurodegeneration as a basic biological principle and may allow additional genetic analyses of the underlying molecular pathways.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2004
Deposited On:02 Sep 2011 08:52
Last Modified:19 Feb 2018 20:36
Publisher:Society for Neuroscience
ISSN:0270-6474
OA Status:Hybrid
Publisher DOI:https://doi.org/10.1523/JNEUROSCI.0283-04.2004
PubMed ID:15102905

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