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.
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Authors | Chen-Yang He, Ding-Yuan Tian, Si-Han Chen, Wang-Sheng Jin, Yuan Cheng, Jia-Yan Xin, Wei-Wei Li, Gui-Hua Zeng, Cheng-Rong Tan, Jie-Ming Jian, Dong-Yu Fan, Jun-Rong Ren, Yu-Hui Liu, Yan-Jiang Wang, Fan Zeng |
Journal | Neuroscience bulletin
(Neurosci Bull)
Vol. 39
Issue 2
Pg. 261-272
(Feb 2023)
ISSN: 1995-8218 [Electronic] Singapore |
PMID | 35974288
(Publication Type: Journal Article)
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Copyright | © 2022. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences. |
Chemical References |
- Receptor, Nerve Growth Factor
- Amyloid beta-Peptides
- Autoantibodies
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Topics |
- Mice
- Animals
- Alzheimer Disease
(pathology)
- Receptor, Nerve Growth Factor
- Amyloid beta-Peptides
- Autoantibodies
- Mice, Transgenic
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