Iijima Koichi, Liu Hsin-Ping, Chiang Ann-Shyn, Hearn Stephen A, Konsolaki Mary, Zhong Yi
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6623-8. doi: 10.1073/pnas.0400895101. Epub 2004 Apr 6.
Accumulation of amyloid-beta (Abeta) peptides in the brain has been suggested to be the primary event in sequential progression of Alzheimer's disease (AD). Here, we use Drosophila to examine whether expression of either the human Abeta40 or Abeta42 peptide in the Drosophila brain can induce pathological phenotypes resembling AD. The expression of Abeta42 led to the formation of diffused amyloid deposits, age-dependent learning defects, and extensive neurodegeneration. In contrast, expression of Abeta40 caused only age-dependent learning defects but did not lead to the formation of amyloid deposits or neurodegeneration. These results strongly suggest that accumulation of Abeta42 in the brain is sufficient to cause behavioral deficits and neurodegeneration. Moreover, Drosophila may serve as a model for facilitating the understanding of molecular mechanisms underlying Abeta toxicity and the discovery of novel therapeutic targets for AD.
大脑中β淀粉样蛋白（Aβ）肽的积累被认为是阿尔茨海默病（AD）连续进展过程中的主要事件。在此，我们利用果蝇来研究在果蝇大脑中表达人Aβ40或Aβ42肽是否能诱导出类似于AD的病理表型。Aβ42的表达导致了弥漫性淀粉样沉积物的形成、年龄依赖性学习缺陷以及广泛的神经退行性变。相比之下，Aβ40的表达仅导致年龄依赖性学习缺陷，但未导致淀粉样沉积物的形成或神经退行性变。这些结果有力地表明，大脑中Aβ42的积累足以导致行为缺陷和神经退行性变。此外，果蝇可作为一个模型，有助于理解Aβ毒性的分子机制以及发现AD的新治疗靶点。
