Elevated Levels of Naturally-Occurring Autoantibodies Against the Extracellular Domain of p75NTR Aggravate the Pathology of Alzheimer's Disease.
- Author:
Chen-Yang HE
1
;
Ding-Yuan TIAN
1
;
Si-Han CHEN
1
;
Wang-Sheng JIN
1
;
Yuan CHENG
1
;
Jia-Yan XIN
1
;
Wei-Wei LI
1
;
Gui-Hua ZENG
1
;
Cheng-Rong TAN
1
;
Jie-Ming JIAN
1
;
Dong-Yu FAN
1
;
Jun-Rong REN
1
;
Yu-Hui LIU
1
;
Yan-Jiang WANG
2
;
Fan ZENG
3
Author Information
- Publication Type:Journal Article
- Keywords: Alzheimer’s disease; Amyloid-beta; Autoantibody; Extracellular domain; Immunity; p75 neurotrophin receptor
- MeSH: Mice; Animals; Alzheimer Disease/pathology*; Receptor, Nerve Growth Factor; Amyloid beta-Peptides; Autoantibodies; Mice, Transgenic
- From: Neuroscience Bulletin 2023;39(2):261-272
- CountryChina
- Language:English
- Abstract: The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.
