In Vivo Pharmacology, Merz Pharmaceuticals GmbH, Eckenheimer Landstrasse 100, D-60318 Frankfurt am Main, Germany.
Behav Brain Res. 2011 Dec 1;225(2):623-41. doi: 10.1016/j.bbr.2011.08.024. Epub 2011 Aug 22.
A better understanding of Alzheimer's disease (AD) and the development of disease modifying therapies are some of the biggest challenges of the 21st century. One of the core features of AD are amyloid plaques composed of amyloid-beta (Aβ) peptides. The first hypothesis proposed that cognitive deficits are linked to plaque-development and transgenic mice have been generated to study this link, thereby providing a good model to develop new therapeutic approaches. Since later it was recognised that in AD patients the cognitive deficit is rather correlated to soluble amyloid levels, consequently, a new hypothesis appeared associating the earliest amyloid toxicity to these soluble species. The purpose of this review is to give a summary of behavioural and cellular data obtained after soluble Aβ peptide administration into rodents' brain, thereby showing that this model is a valid tool to investigate AD pathology when no plaques are present. Additionally, this method offers an excellent, efficient model to test compounds which could act at such early stages of the disease.
更好地了解阿尔茨海默病（AD）和开发疾病修饰疗法是 21 世纪最大的挑战之一。AD 的核心特征之一是由淀粉样β（Aβ）肽组成的淀粉样斑块。第一个假设提出认知缺陷与斑块形成有关，为此已经产生了转基因小鼠来研究这种联系，从而为开发新的治疗方法提供了一个很好的模型。后来人们认识到，在 AD 患者中，认知缺陷与可溶性淀粉样蛋白水平相关性更强，因此，出现了一个新的假设，将与最早的淀粉样毒性相关的可溶性物质与之关联。本文的目的是总结可溶性 Aβ 肽给药后在啮齿动物大脑中获得的行为和细胞数据，从而表明当没有斑块时，该模型是研究 AD 病理的有效工具。此外，这种方法提供了一个极好的、有效的模型来测试可能在疾病早期发挥作用的化合物。
