Matsumoto Shin-Ei, Jin Haifeng, Takeda Kazuya, Hasegawa Yukako, Motoi Yumiko, Hattori Nobutaka, Tabira Takeshi
Department of Diagnosis, Prevention and Treatment of Dementia, Graduate School of Medicine, Juntendo University.
Rinsho Shinkeigaku. 2012;52(11):1168-70. doi: 10.5692/clinicalneurol.52.1168.
Based on the amyloid cascade hypothesis, immunotherapy targeting amyloid β (Aβ) for Alzheimer's disease (AD) has been developed. It was reported that active immunization using Aβ peptide attenuates amyloid deposits and memory impairment in AD model mice. However, active immunization of patients with AD (AN-1792) was halted due to adverse effects in which a subset of patients developed meningoencephalitis. In order to avoid autoimmune encephalitis, passive immunotherapy using humanized monoclonal antibodies with specificity to Aβ are in clinical trials. We also developed an anti-Aβ monoclonal antibody 3.4A10, which react with AD brain-specific Aβ oligomers. On the other hand, some studies showed that immunotherapy approach targeting tau could attenuate pathology in AD model mouse. Here we introduce a current trend of immunotherapy for AD.
基于淀粉样蛋白级联假说,已开发出针对阿尔茨海默病(AD)的靶向淀粉样β(Aβ)的免疫疗法。据报道,使用Aβ肽进行主动免疫可减轻AD模型小鼠的淀粉样蛋白沉积和记忆障碍。然而,AD患者的主动免疫(AN - 1792)因不良反应而停止,部分患者出现了脑膜脑炎。为避免自身免疫性脑炎,使用对Aβ具有特异性的人源化单克隆抗体的被动免疫疗法正在进行临床试验。我们还开发了一种抗Aβ单克隆抗体3.4A10,它能与AD脑特异性Aβ寡聚体发生反应。另一方面,一些研究表明,针对tau的免疫疗法可减轻AD模型小鼠的病理变化。在此,我们介绍AD免疫疗法的当前趋势。