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

2004; Society for Neuroscience; Volume: 24; Issue: 16 Linguagem: Inglês

10.1523/jneurosci.0283-04.2004

1529-2401

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

Cholinesterase and Neurodegenerative Diseases

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, theβ-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.