Naturally-Occurring Antibodies Against Bim are Decreased in Alzheimer's Disease and Attenuate AD-type Pathology in a Mouse Model

作者全名："Jian, Jie-Ming; Fan, Dong-Yu; Tian, Ding-Yuan; Cheng, Yuan; Sun, Pu-Yang; Tan, Cheng-Rong; Zeng, Gui-Hua; He, Chen-Yang; Wang, Ye-Ran; Zhu, Jie; Yao, Xiu-Qing; Wang, Yan-Jiang; Liu, Yu-Hui"

作者地址："[Jian, Jie-Ming; Fan, Dong-Yu; Tian, Ding-Yuan; Cheng, Yuan; Sun, Pu-Yang; Tan, Cheng-Rong; Zeng, Gui-Hua; He, Chen-Yang; Wang, Ye-Ran; Zhu, Jie; Wang, Yan-Jiang; Liu, Yu-Hui] Third Mil Med Univ, Daping Hosp, Dept Neurol, Chongqing 400000, Peoples R China; [Jian, Jie-Ming; Fan, Dong-Yu; Tian, Ding-Yuan; Cheng, Yuan; Sun, Pu-Yang; Tan, Cheng-Rong; Zeng, Gui-Hua; He, Chen-Yang; Wang, Ye-Ran; Zhu, Jie; Wang, Yan-Jiang; Liu, Yu-Hui] Third Mil Med Univ, Daping Hosp, Ctr Clin Neurosci, Chongqing 400000, Peoples R China; [Fan, Dong-Yu] Third Mil Med Univ, Xinqiao Hosp, Shigatse Branch, Shigatse 857000, Peoples R China; [Yao, Xiu-Qing] Chongqing Med Univ, Dept Rehabil, Affiliated Hosp 2, Chongqing 400000, Peoples R China; [Wang, Yan-Jiang] Key Lab Ageing & Brain Dis, Chongqing 400000, Peoples R China; [Wang, Yan-Jiang] Chinese Acad Sci, Ctr Excellence Brain Sci & Intelligence Technol, Shanghai 200031, Peoples R China"

通信作者："Wang, YJ; Liu, YH (通讯作者)，Third Mil Med Univ, Daping Hosp, Dept Neurol, Chongqing 400000, Peoples R China.; Wang, YJ; Liu, YH (通讯作者)，Third Mil Med Univ, Daping Hosp, Ctr Clin Neurosci, Chongqing 400000, Peoples R China.; Wang, YJ (通讯作者)，Key Lab Ageing & Brain Dis, Chongqing 400000, Peoples R China.; Wang, YJ (通讯作者)，Chinese Acad Sci, Ctr Excellence Brain Sci & Intelligence Technol, Shanghai 200031, Peoples R China."

来源：NEUROSCIENCE BULLETIN

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000795763800004

JCR分区：Q2

影响因子：5.6

年份：2022

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Alzheimer's disease; Amyloid-beta; Bim; Naturally-occurring antibodies; Neuronal apoptosis

摘要："Increased neuronal apoptosis is an important pathological feature of Alzheimer's disease (AD). The Bcl-2-interacting mediator of cell death (Bim) mediates amyloid-beta (A beta)-induced neuronal apoptosis. Naturally-occurring antibodies against Bim (NAbs-Bim) exist in human blood, with their levels and functions unknown in AD. In this study, we found that circulating NAbs-Bim were decreased in AD patients. Plasma levels of NAbs-Bim were negatively associated with brain amyloid burden and positively associated with cognitive functions. Furthermore, NAbs-Bim purified from intravenous immunoglobulin rescued the behavioral deficits and ameliorated A beta deposition, tau hyperphosphorylation, microgliosis, and neuronal apoptosis in APP/PS1 mice. In vitro investigations demonstrated that NAbs-Bim were neuroprotective against AD through neutralizing Bim-directed neuronal apoptosis and the amyloidogenic processing of amyloid precursor protein. These findings indicate that the decrease of NAbs-Bim might contribute to the pathogenesis of AD and immunotherapies targeting Bim hold promise for the treatment of AD."

基金机构："National Natural Science Foundation of China [81930028, 81971024, 81971033]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (81930028, 81971024, and 81971033)."