The mechanisms and consequences of plaque removal following Abeta immunotherapy in human Alzheimer's disease

人类阿尔茨海默病 Abeta 免疫治疗后斑块去除的机制和后果

• 批准号: G0501033/1
• 负责人: Delphine Boche
• 金额: $ 30.12万
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0501033%2F1
• 关键词: mechanisms; consequences; plaque; removal; following

Alzheimer’s disease (AD) is the commonest cause of dementia in old age. In AD a protein known as amyloid-beta (A?) accumulates in the brain regions critical for learning and memory.Recently in animal studies immunization with A? has been shown to result in removal of A? from the brain associated with improvement in brain function. Some preliminary results of the initial human clinical trials suggested a slower cognitive deterioration in patients with an appropriate immune response.The precise mechanism by which the activated immune system removes Ab is as yet unclear. Furthermore, some patients developed cerebral inflammatory complications, halting the clinical trials. Access to post mortem brain tissue from patients participating in the clinical trial of Ab immunotherapy puts us in a unique position to address important questions. We aim to clarify: (i) the mechanism(s) of Ab plaque removal (ii) if plaque removal can take place without the unwanted side effects of severe cerebral inflammation and (iii) the consequences of Ab removal on the other features of AD pathology.This information is important in order to inform the second generation of trials of Ab immunotherapy which are already underway.

阿尔茨海默病（AD）是老年痴呆症最常见的原因。在AD中，一种称为淀粉样蛋白β（A？）积累在大脑区域的学习和记忆的关键。最近在动物研究免疫接种A？已被证明可以去除A？与脑功能的改善有关。最初的人体临床试验的一些初步结果表明，在适当的免疫反应下，患者的认知能力下降较慢。激活的免疫系统清除Ab的确切机制尚不清楚。此外，一些患者出现了脑炎症并发症，停止了临床试验。从参与Ab免疫治疗临床试验的患者中获得死后脑组织使我们处于解决重要问题的独特地位。我们的目的是澄清：（i）Ab斑块去除的机制（ii）斑块去除是否可以在没有严重脑炎症的不希望的副作用的情况下进行，以及（iii）Ab去除对AD病理学的其他特征的后果。