中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (2): 577-587.doi: 10.4103/NRR.NRR-D-24-00846

• 综述:退行性病与再生 • 上一篇    下一篇

针对Aβ和tau免疫治疗阿尔茨海默病的进展

  

  • 出版日期:2026-02-15 发布日期:2025-05-22

Recent advances in immunotherapy targeting amyloidbeta and tauopathies in Alzheimer’s disease

Sha Sha1, #, Lina Ren1, #, Xiaona Xing2 , Wanshu Guo3 , Yan Wang1 , Ying Li1 , Yunpeng Cao4 , Le Qu5, *   

  1. 1 Department of Geriatrics, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China;  2 Department of Neurology, Shenzhen Luohu People’s Hospital, The Third Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province, China;  3 Department of Neurology, People’s Hospital of Liaoning Province, Shenyang, Liaoning Province, China;  4 Department of Neurology, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China;  5 Department of Dermatology, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
  • Online:2026-02-15 Published:2025-05-22
  • Contact: Le Qu, PhD, cmuqule@163.com.
  • Supported by:
    This work was supported by the Nature Science Foundation of Liaoning Province, Nos. 2022-MS-211, 2021-MS-064, and 2024-MS-048 (all to YC).

摘要:

阿尔茨海默病是一种以渐进性认知能力下降为特征的毁灭性神经退行性疾病,其病理是Aβ蛋白沉积和tau蛋白磷酸化。有效减少Aβ42聚集体和tau寡聚体的细胞毒性可能延缓阿尔茨海默病进展。常规的美金刚等药物只能缓解症状,并不能预防病理过程或认知恶化。目前,针对Aβ和tau的主动和被动免疫对无症状阿尔茨海默病小鼠以及其他阿尔茨海默病转基因动物模型显示出一定疗效,因而引起人们的关注,但是在发现Lecanemab和Donanemab前,阿尔茨海默病的主动和被动免疫治疗的临床转化都收效甚微。因此,此次综述首先回顾了阿尔茨海默病的病理学研究进展以及针对Aβ和tau蛋白的主动和被动免疫治疗方法,并讨论不同免疫治疗方法的优缺点,以及未来免疫治疗的前景。尽管一些抗体药物在早期阿尔茨海默病患者中显示出希望,但仍需大量临床数据验证其在中期患者中的效果。

https://orcid.org/0000-0002-6923-5364 (Le Qu)

关键词: 免疫疗法, 淀粉样蛋白β, tau蛋白过度磷酸化, 低聚物, 阿尔茨海默病, 认知功能障碍, 淀粉样沉积, 预防性免疫接种, 痴呆, 抗体

Abstract: Alzheimer’s disease, a devastating neurodegenerative disorder, is characterized by progressive cognitive decline, primarily due to amyloid-beta protein deposition and tau protein phosphorylation. Effectively reducing the cytotoxicity of amyloid-beta42 aggregates and tau oligomers may help slow the progression of Alzheimer’s disease. Conventional drugs, such as donepezil, can only alleviate symptoms and are not able to prevent the underlying pathological processes or cognitive decline. Currently, active and passive immunotherapies targeting amyloid-beta and tau have shown some efficacy in mice with asymptomatic Alzheimer’s disease and other transgenic animal models, attracting considerable attention. However, the clinical application of these immunotherapies demonstrated only limited efficacy before the discovery of lecanemab and donanemab. This review first discusses the advancements in the pathogenesis of Alzheimer’s disease and active and passive immunotherapies targeting amyloid-beta and tau proteins. Furthermore, it reviews the advantages and disadvantages of various immunotherapies and considers their future prospects. Although some antibodies have shown promise in patients with mild Alzheimer’s disease, substantial clinical data are still lacking to validate their effectiveness in individuals with moderate Alzheimer’s disease.

Key words: Alzheimer’s disease, amyloid deposits, amyloid-beta, antibody, cognitive dysfunction, dementia, immunotherapy, oligomer, preventive immunization, tau hyperphosphorylation