Elevated Levels of Naturally-Occurring Autoantibodies Against the Extracellular Domain of p75NTR Aggravate the Pathology of Alzheimer's Disease / 神经科学通报·英文版
Neuroscience Bulletin
; (6): 261-272, 2023.
Article
Dans En
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| ID: wpr-971551
Responsable en Bibliothèque :
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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.
Texte intégral:
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Indice:
WPRIM
Sujet Principal:
Autoanticorps
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Souris transgéniques
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Peptides bêta-amyloïdes
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Récepteur facteur croissance nerf
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Maladie d'Alzheimer
Limites du sujet:
Animals
langue:
En
Texte intégral:
Neuroscience Bulletin
Année:
2023
Type:
Article