Fc effector of anti-A beta 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, Xiao-ying3,4; Yu, Xiao-lin1,3; Zhu, Jie3,4; Li, Ling-jie3,4; Zhang, Lun1,3; Huang, Ya-ru3,4; Liu, Dong-qun3; Ji, Mei3; Sun, Xun3; Zhang, Ling-xiao3 |
| 刊名 | SIGNAL TRANSDUCTION AND TARGETED THERAPY
 |
| 出版日期 | 2023-01-25 |
| 卷号 | 8期号:1页码:14 |
| ISSN号 | 2095-9907 |
| DOI | 10.1038/s41392-022-01273-8 |
| 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 A beta-targeting antibodies including their lgG1 and lgG4 subtypes induced microglial engulfment of neuronal synapses by activating CR3 or Fc gamma RIIb via the complex of A beta, antibody, and complement. Notably, anti-A beta antibodies without Fc fragment, or with blockage of CR3 or Fc gamma RIIb, did not exert these adverse effects. Consistently, A beta-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, A beta-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. |
| WOS关键词 | SCFV ANTIBODY ; MICROGLIA ; COMPLEMENT ; INSIGHTS ; BAPINEUZUMAB ; MECHANISMS ; HEALTH |
| 资助项目 | Strategic Priority Research Program of the Chinese Academy of Sciences[XDB39050600] ; National Natural Science Foundation of China[82150107] ; National Natural Science Foundation of China[81971610] ; foundation of Innovation Academy for Green Manufacture Institute, Chinese Academy of Sciences[IAGM2020C29] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000922348700002 |
| 出版者 | SPRINGERNATURE |
| 资助机构 | Strategic Priority Research Program of the Chinese Academy of Sciences ; National Natural Science Foundation of China ; foundation of Innovation Academy for Green Manufacture Institute, Chinese Academy of Sciences |
| 源URL | [http://ir.ipe.ac.cn/handle/122111/56996]  |
| 通讯作者 | Yu, Xiao-lin; Liu, Rui-tian |
| 作者单位 | 1.Chinese Acad Sci, Innovat Acad Green Manufacture Inst, Beijing 100190, Peoples R China 2.Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing 100101, Peoples R China 3.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China 4.Univ Chinese Acad Sci, Sch Chem & Chem Engn, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Sun, Xiao-ying,Yu, Xiao-lin,Zhu, Jie,et al. Fc effector of anti-A beta antibody induces synapse loss and cognitive deficits in Alzheimer's disease-like mouse model[J]. SIGNAL TRANSDUCTION AND TARGETED THERAPY,2023,8(1):14. |
| APA | Sun, Xiao-ying.,Yu, Xiao-lin.,Zhu, Jie.,Li, Ling-jie.,Zhang, Lun.,...&Liu, Rui-tian.(2023).Fc effector of anti-A beta antibody induces synapse loss and cognitive deficits in Alzheimer's disease-like mouse model.SIGNAL TRANSDUCTION AND TARGETED THERAPY,8(1),14. |
| MLA | Sun, Xiao-ying,et al."Fc effector of anti-A beta antibody induces synapse loss and cognitive deficits in Alzheimer's disease-like mouse model".SIGNAL TRANSDUCTION AND TARGETED THERAPY 8.1(2023):14. |
入库方式： OAI收割
来源：过程工程研究所
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