阿尔茨海默病Aβ免疫治疗的机制
The mechanism of Aβ immunotherapy for Alzheimer's disease
摘要
Abstract
Alzheimer's disease(AD)is a neurodegenerative disease characterized primarily by two core pathological features:abnormal deposition of β-amyloid(Aβ)around neurons in the cerebral cortex and hippocampus,and hyperphosphorylation of Tau protein.Based on the understanding that Aβ is derived from the pathological cleavage of amyloid precursor protein(APP)—and that Aβ exerts its pathogenic effects by damaging mitochondria,impairing synapses,and triggering neuroinflammation-this article notes that existing pharmacotherapies only alleviate symptoms.In contrast,Aβ immunotherapy has emerged as a key disease-modifying therapeutic strategy for AD,and immunotherapies targeting Aβ have become an important direction in AD disease-modifying therapy(DMT).This article systematically reviews the core mechanisms of Aβ immunotherapy,including the multi-dimensional roles of the immune system(such as Aβ clearance,inflammation regulation,and neuroprotection),as well as the characteristics of two major types of immunotherapies:passive immunotherapy with exogenous anti-Aβ monoclonal antibodies(such as Lecanemab and Donanemab),which take effect by activating phagocytosis and destroying plaques;and active immunotherapy,which induces antibodies through Aβ vaccines.New-generation vaccines optimize epitopes and adjuvants and have preventive potential.Additionally,the article provides an outlook on the clinical progress and future challenges of AD.关键词
阿尔茨海默病(AD)/疾病修饰治疗/免疫治疗/Aβ清除机制Key words
Alzheimer's disease(AD)/disease-modifying treatment/immunotherapy/the Aβ clearance mechanism分类
医药卫生引用本文复制引用
姚丹,李川,杜婴,张巍..阿尔茨海默病Aβ免疫治疗的机制[J].西安交通大学学报（医学版）,2026,47(1):10-17,8.基金项目
国家自然科学基金资助项目(No.82571606,No.82171406,No.82271457) （No.82571606,No.82171406,No.82271457）
陕西省卫健委-卫生健康认知功能障碍科研创新团队(No.2023TD-06) （No.2023TD-06）
陕西省科技厅-阿尔茨海默病新型生物标志物及其靶向治疗研究创新团队(No.2024RS-CXTD-87) （No.2024RS-CXTD-87）
西安市医学研究重点项目-阿尔茨海默病免疫诊治新方法和关键技术的研究(No.2024JH-YXZD-0047) （No.2024JH-YXZD-0047）
空军军医大学临床研究项目-认知功能障碍生物样本库专项建设(No.2024LC2440)Supported by the National Natural Science Foundation of China(No.82571606,No.82171406,No.82271457),Shaanxi Provincial Health Research and Innovation Team for Cognitive Dysfunction Disease(No.2023TD-06),Shaanxi Innovative Team for Science and Technology(No.2024RS-CXTD-87),Key Research Project of Xi'an Medical Research-Research on New Methods and Key Technolo-gies for Immunodiagnosis and Immunotherapy of Alzheimer's Disease(No.2024JH-YXZD-0047),and The Construction of a Special-ized Biobank for Cognitive Dysfunction in the Clinical Research Project of Air Force Military Medical University(No.2024LC2440) （No.2024LC2440）
