Age-dependent Neurodegeneration and Alzheimer-amyloid Plaque Formation in Transgenic Drosophila

Overview

Journal J Neurosci

Specialty Neurology

Date 2004 Apr 23

PMID 15102905

Citations 135

Authors

Isabell Greeve

Doris Kretzschmar

Jakob-Andreas Tschape

Anika Beyn

Claire Brellinger

Michaela Schweizer

Roger M Nitsch

Rita Reifegerste

Affiliations

Soon will be listed here.

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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