Naturally-Occurring Antibodies Against Bim are Decreased in Alzheimer's Disease and Attenuate AD-type Pathology in a Mouse Model.
10.1007/s12264-022-00869-y
- Author:
Jie-Ming JIAN
1
;
Dong-Yu FAN
1
;
Ding-Yuan TIAN
1
;
Yuan CHENG
1
;
Pu-Yang SUN
1
;
Cheng-Rong TAN
1
;
Gui-Hua ZENG
1
;
Chen-Yang HE
1
;
Ye-Ran WANG
1
;
Jie ZHU
1
;
Xiu-Qing YAO
2
;
Yan-Jiang WANG
3
;
Yu-Hui LIU
4
Author Information
1. Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, 400000, China.
2. Department of Rehabilitation, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400000, China.
3. Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, 400000, China. yanjiang_wang@tmmu.edu.cn.
4. Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, 400000, China. yuhuiliu@tmmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Alzheimer’s disease;
Amyloid-beta;
Bim;
Naturally-occurring antibodies;
Neuronal apoptosis
- MeSH:
Alzheimer Disease/pathology*;
Amyloid beta-Peptides/metabolism*;
Amyloid beta-Protein Precursor/metabolism*;
Animals;
Disease Models, Animal;
Humans;
Mice;
Mice, Transgenic
- From:
Neuroscience Bulletin
2022;38(9):1025-1040
- CountryChina
- Language:English
-
Abstract:
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 (Aβ)-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 Aβ 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.
