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适应性免疫反应在阿尔茨海默病中的新作用

Emerging Roles of Adaptive Immune Response in Alzheimer's Disease.

作者信息

Li Cong, Zhao Qinghe, Feng Lina, Li Mingquan

机构信息

College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.

出版信息

Aging Dis. 2024 Aug 14. doi: 10.14336/AD.2024.0564.

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by progressive cognitive decline. Pathologically, this disease is associated with the accumulation of extracellular amyloid plaques, intracellular neurofibrillary tangles (NFTs), and neuroinflammation. Current drug treatments primarily focus on managing symptoms rather than stopping disease progression. Disease-modifying therapies target the clearance of amyloid plaques through active and passive immunity methods. Although successful in animal models, human trials have shown adverse effects, such as meningoencephalitis, in a small number of patients who received active immunity methods. The efficacy of active immunity methods in treating AD remains uncertain, but passive immunity methods amyloid-beta (Abeta)-specific monoclonal antibody therapies such as aducanumab and lecanemab have been approved by the FDA. Despite the limitations of immune-based therapies, T-cell, and chimeric antigen receptor-based treatments show promise, but new guidelines are necessary to address potential adverse events. Research into the relationship between adaptive immune responses and AD is expected to provide innovative treatment approaches.

摘要

阿尔茨海默病(AD)是最常见的神经退行性疾病,其特征是进行性认知衰退。在病理上,这种疾病与细胞外淀粉样斑块、细胞内神经原纤维缠结(NFTs)以及神经炎症的积累有关。目前的药物治疗主要侧重于控制症状,而非阻止疾病进展。疾病修饰疗法通过主动免疫和被动免疫方法来清除淀粉样斑块。尽管在动物模型中取得了成功,但人体试验表明,少数接受主动免疫方法的患者出现了不良反应,如脑膜脑炎。主动免疫方法治疗AD的疗效仍不确定,但被动免疫方法,如阿杜卡单抗和乐卡奈单抗等β淀粉样蛋白(Aβ)特异性单克隆抗体疗法已获得美国食品药品监督管理局(FDA)的批准。尽管基于免疫的疗法存在局限性,但基于T细胞和嵌合抗原受体的治疗显示出前景,但需要新的指南来应对潜在的不良事件。对适应性免疫反应与AD之间关系的研究有望提供创新的治疗方法。

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