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Amyloid Abeta in the natural history of Alzheimer's disease

阿尔茨海默病自然史中的淀粉样蛋白 Abeta

基本信息

批准号：
nhmrc : 145632
负责人：
Prof Catriona Mclean
金额：
$ 14.7万
依托单位：
依托单位国家：
澳大利亚
项目类别：
NHMRC Project Grants
财政年份：
2001
资助国家：
澳大利亚
起止时间：
2001-01-01 至 2002-12-31
项目状态：
已结题

来源：
https://researchdata.edu.au/amyloid-abeta-natural-alzheimers-disease/77432
关键词：
Amyloid Abeta natural history Alzheimer

项目摘要

This grant is the continuation of a large series of experiments designed to uncover the basic causes of Alzheimer's disease. The focus is on closing some of the gaps in our knowledge of the natural history of Alzheimer's disease in relation to the deposition of the Abeta amyloid protein in the brain, which we believe plays a central role in the degeneration of nerve cells in this condition. The main questions we are tackling include: the feasibility of using assays of Abeta in the blood as a biological marker of Alzheimer's disease; whether better transgenic mouse models of Alzheimer's disease are required; whether the soluble forms of Abeta amyloid are the major species which cause neurotoxicity (in contrast to the insoluble forms which constitute the bulk of this protein in the Alzheimer's disease brain); and whether the intracellular or extracellular pathways of Abeta aggregation and toxicity are the key to understanding this disease. Increasing evidence suggests that the clearance of soluble forms of the Abeta protein from the brain may be a major therapeutic strategy. We therefore require further investigations of how these soluble forms of Abeta are generated in nerve cells, and how these forms exist in equilibrium with soluble and insoluble pools in the brain, cerebrospinal fluid, blood and other tissues of the body.

这项资助是一系列旨在揭示阿尔茨海默病基本原因的实验的继续。重点是缩小我们对阿尔茨海默病自然史的认识中的一些空白，这些知识与大脑中Abeta淀粉样蛋白的沉积有关，我们认为Abeta淀粉样蛋白在这种情况下神经细胞的变性中起着核心作用。我们正在解决的主要问题包括：使用血液中Abeta作为阿尔茨海默病生物标志物的可行性;是否需要更好的阿尔茨海默病转基因小鼠模型; Abeta淀粉样蛋白的可溶形式是否是导致神经毒性的主要物种（与构成阿尔茨海默病脑中这种蛋白质的大部分的不溶性形式相反）;以及Abeta聚集和毒性的细胞内或细胞外途径是理解这种疾病的关键。越来越多的证据表明，从大脑中清除可溶性形式的Abeta蛋白可能是一种主要的治疗策略。因此，我们需要进一步研究这些可溶性形式的Abeta是如何在神经细胞中产生的，以及这些形式如何与大脑，脑脊液，血液和身体其他组织中的可溶性和不溶性池平衡存在。