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

作者：Greeve I; Kretzschmar D; Tschape JA; Beyn A; Brellinger C; Schweizer M; Nitsch RM; Reifegerste R^*

来源：Journal of Neuroscience, 2004, 24(16): 3899-3906.

DOI：10.1523/JNEUROSCI.0283-04.2004

• Alzheimer
• dementia
• aging
• neuropathology
• degeneration
• Drosophila

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.

• 出版日期2004-4-21