靶向β-淀粉样蛋白的阿尔茨海默病免疫治疗研究进展

Immunotherapy targeting β-amyloid for Alzheimer′s disease:research advances

阿尔茨海默病是一种以认知功能障碍和记忆减退为主要特征的神经退行性疾病,主要神经病理学表现包括细胞外淀粉样蛋白堆积形成的老年斑、细胞内tau蛋白磷酸化形成的神经原纤维缠结,以及神经元的坏死。淀粉样蛋白级联假说认为,β-淀粉样蛋白的过量生成和积累是阿尔茨海默病致病的始发因素和中心环节。以β-淀粉样蛋白为靶标的主动免疫和被动免疫方法可能是最有希望治疗阿尔茨海默病的策略之一。本综述主要关注以β-淀粉样蛋白为靶标的阿尔茨海默病主动和被动免疫治疗方法,分析目前临床前研究和临床试验结果,探讨该领域的应用前景和发展方向,提出新一代有效疫苗的设计策略。

Alzheimer′s disease（AD）is a neurodegenerative disorder that impairs memory and cognition. The neuropathological features of the disease include neurofibrillary tangles,deposition of β-amyloid（Aβ）in senile plaques and neuronal loss in affected brain regions. The amyloid cascade hypothesis suggests that production and accumulation of excessive β- amyloid may be the main cause of the onset and progression of Alzheimer′s disease. Active and passive immunotherapy targeting β-amyloid may be the most promising strategy to prevent or treat AD. This review seeks to put perspective to the mixed results obtained so far in pre-clinical and clinical trials of AD vaccines and antibodies targeting β-amyloid and discusses the perspective and novel direction of successful AD immunotherapy. Novel strategies for the design of more effective therapeutic vaccines are suggested.