Sha Sha, Ren Lina, Xing Xiaona, Guo Wanshu, Wang Yan, Li Ying, Cao Yunpeng, Qu Le
Department of Geriatrics, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
Department of Neurology, Shenzhen Luohu People's Hospital, The Third Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province, China.
Neural Regen Res. 2026 Feb 1;21(2):577-587. doi: 10.4103/NRR.NRR-D-24-00846. Epub 2025 Jan 29.
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.
阿尔茨海默病是一种毁灭性的神经退行性疾病，其特征是进行性认知衰退，主要原因是β-淀粉样蛋白沉积和tau蛋白磷酸化。有效降低β-淀粉样蛋白42聚集体和tau寡聚体的细胞毒性可能有助于减缓阿尔茨海默病的进展。传统药物，如多奈哌齐，只能缓解症状，无法预防潜在的病理过程或认知衰退。目前，针对β-淀粉样蛋白和tau的主动和被动免疫疗法在无症状阿尔茨海默病小鼠和其他转基因动物模型中已显示出一定疗效，引起了广泛关注。然而，在发现lecanemab和donanemab之前，这些免疫疗法的临床应用仅显示出有限的疗效。本文首先讨论了阿尔茨海默病发病机制以及针对β-淀粉样蛋白和tau蛋白的主动和被动免疫疗法的进展。此外，还综述了各种免疫疗法的优缺点，并展望了其未来前景。尽管一些抗体在轻度阿尔茨海默病患者中显示出了前景，但仍缺乏大量临床数据来验证其在中度阿尔茨海默病患者中的有效性。
