Guo Xiaoyi, Yan Li, Zhang Denghong, Zhao Yingjun
Center for Brain Sciences, the First Affiliated Hospital of Xiamen University, Institute of Neuroscience, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China.
School of Traditional Chinese Medicine, Jinan University, 601 Huangpu Avenue West, Guangzhou, Guangdong 510632, China.
Ageing Res Rev. 2024 Feb;94:102192. doi: 10.1016/j.arr.2024.102192. Epub 2024 Jan 14.
Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by cognitive impairment with few therapeutic options. Despite many failures in developing AD treatment during the past 20 years, significant advances have been achieved in passive immunotherapy of AD very recently. Here, we review characteristics, clinical trial data, and mechanisms of action for monoclonal antibodies (mAbs) targeting key players in AD pathogenesis, including amyloid-β (Aβ), tau and neuroinflammation modulators. We emphasized the efficacy of lecanemab and donanemab on cognition and amyloid clearance in AD patients in phase III clinical trials and discussed factors that may contribute to the efficacy and side effects of anti-Aβ mAbs. In addition, we provided important information on mAbs targeting tau or inflammatory regulators in clinical trials, and indicated that mAbs against the mid-region of tau or pathogenic tau have therapeutic potential for AD. In conclusion, passive immunotherapy targeting key players in AD pathogenesis offers a promising strategy for effective AD treatment.
阿尔茨海默病（AD）是最常见的神经退行性疾病，其特征为认知障碍，治疗选择有限。尽管在过去20年中AD治疗的研发多次失败，但最近在AD的被动免疫疗法方面取得了重大进展。在此，我们综述了针对AD发病机制中的关键因子（包括淀粉样β蛋白（Aβ）、tau蛋白和神经炎症调节剂）的单克隆抗体（mAb）的特性、临床试验数据及作用机制。我们强调了lecanemab和donanemab在III期临床试验中对AD患者认知和淀粉样蛋白清除的疗效，并讨论了可能影响抗Aβ mAb疗效和副作用的因素。此外，我们提供了关于临床试验中靶向tau蛋白或炎症调节剂的mAb的重要信息，并指出针对tau蛋白中部区域或致病性tau蛋白的mAb对AD具有治疗潜力。总之，针对AD发病机制中的关键因子进行被动免疫疗法为AD的有效治疗提供了一个有前景的策略。
