首页|Elevated Levels of Naturally-Occurring Autoantibodies Against the Extracellular Domain of p75NTR Aggravate the Pathology of Alzheimer's Disease

Elevated Levels of Naturally-Occurring Autoantibodies Against the Extracellular Domain of p75NTR Aggravate the Pathology of Alzheimer's Disease

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The extracellular domain(p75ECD)of p75 neu-rotrophin 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 pres-ence 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.

Alzheimer's diseasep75 neurotrophin receptorExtracellular domainAutoantibodyAmyloid-betaImmunity

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

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Department of Neurology and Center for Clinical Neuroscience,Daping Hospital,Third Military Medical University,Chongqing 400042,China

Department of Neurology,The General Hospital of Western Theater Command,Chengdu 610000,China

Department of Cardiology,Southwest Hospital,Third Military Medical University,Chongqing 400042,China

Department of Neurology,Nanchong Central Hospital,The Second Clinical Medical School,North Sichuan Medical College,Nanchong 637000,China

Chongqing Key Laboratory of Ageing and Brain Diseases,Chongqing 400042,China

Department of Clinical Medicine,North Sichuan Medical College,Nanchong 637000,China

Shigatse Branch,Xinqiao Hospital,Third Military Medical University,Shigatse 857000,China

The Institute of Brain and Intelligence,Third Military Medical University,Chongqing 400042,China

State Key Laboratory of Trauma.Burn and Combined Injury,Daping Hospital,Third Military Medical University,Chongqing 400042,China

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National Natural Science Foundation of China

81870860

2023

10.1007/s12264-022-00936-4

神经科学通报(英文版)
中国科学院上海生命科学研究院

神经科学通报(英文版)

CSTPCDCSCD
影响因子：0.741
ISSN：1673-7067
年,卷(期)：2023.39(2)
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