Fc effector of anti-Aβ antibody induces synapse loss and cognitive deficits in Alzheimer's disease-like mouse model
文献类型：期刊论文
| 作者 | Sun Xiaoying2; Yu Xiaolin2; Zhu Jie2; Li Lingjie2; Zhang Lun2; Huang Yaru2; Liu Dongqun2; Ji Mei2; Sun Xun2; Zhang Lingxiao2 |
| 刊名 | SIGNAL TRANSDUCTION AND TARGETED THERAPY
 |
| 出版日期 | 2023 |
| 卷号 | 8期号:2页码:813 |
| ISSN号 | 2095-9907 |
| 关键词 | Neuroimmunology Neurological disorders |
| 英文摘要 | Passive immunotherapy is one of the most promising interventions for Alzheimer's disease (AD).However,almost all immune-modulating strategies fail in clinical trials with unclear causes although they attenuate neuropathology and cognitive deficits in AD animal models.Here,we showed that Aβ-targeting antibodies including their IgG1 and IgG4 subtypes induced microglial engulfment of neuronal synapses by activating CR3 or FcγRllb via the complex of Aβ,antibody,and complement.Notably,anti-Aβ antibodies without Fc fragment,or with blockage of CR3 or FcγRllb,did not exert these adverse effects.Consistently,Aβ-targeting antibodies,but not their Fab fragments,significantly induced acute microglial synapse removal and rapidly exacerbated cognitive deficits and neuroinflammation in APP/PS1 mice post-treatment,whereas the memory impairments in mice were gradually rescued thereafter.Since the recovery rate of synapses in humans is much lower than that in mice,our findings may clarify the variances in the preclinical and clinical studies assessing AD immunotherapies.Therefore,Aβ-targeting antibodies lack of Fc fragment,or with reduced Fc effector function,may not induce microglial synaptic pruning,providing a safer and more efficient therapeutic alternative for passive immunotherapy for AD. |
| 语种 | 英语 |
| 源URL | [http://ir.ipe.ac.cn/handle/122111/57181]  |
| 作者单位 | 1.中国科学院动物研究所 2.中国科学院过程工程研究所 |
| 推荐引用方式 GB/T 7714 | Sun Xiaoying,Yu Xiaolin,Zhu Jie,et al. Fc effector of anti-Aβ antibody induces synapse loss and cognitive deficits in Alzheimer's disease-like mouse model[J]. SIGNAL TRANSDUCTION AND TARGETED THERAPY,2023,8(2):813. |
| APA | Sun Xiaoying.,Yu Xiaolin.,Zhu Jie.,Li Lingjie.,Zhang Lun.,...&Liu Ruitian.(2023).Fc effector of anti-Aβ antibody induces synapse loss and cognitive deficits in Alzheimer's disease-like mouse model.SIGNAL TRANSDUCTION AND TARGETED THERAPY,8(2),813. |
| MLA | Sun Xiaoying,et al."Fc effector of anti-Aβ antibody induces synapse loss and cognitive deficits in Alzheimer's disease-like mouse model".SIGNAL TRANSDUCTION AND TARGETED THERAPY 8.2(2023):813. |
入库方式： OAI收割
来源：过程工程研究所
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