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

被引：219

作者：

Greeve, I

Kretzschmar, D

Tschäpe, JA

Beyn, A

Brellinger, C

Schweizer, M

Nitsch, RM

Reifegerste, R

机构：

[1] Univ Hamburg, Ctr Mol Neurobiol, D-20251 Hamburg, Germany

[2] Univ Hosp Bern, Inselspital, Dept Neurol, CH-3010 Bern, Switzerland

[3] Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97201 USA

[4] Univ Zurich, Div Psychiat Res, CH-8008 Zurich, Switzerland

[5] Evotec Neurosci GmbH, D-22525 Hamburg, Germany

来源：

JOURNAL OF NEUROSCIENCE | 2004年 / 24卷 / 16期

关键词：

Alzheimer; dementia; aging; neuropathology; degeneration; Drosophila;

D O I：

10.1523/JNEUROSCI.0283-04.2004

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：3899 / 3906

页数：8

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