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

Chen-Yang He ¹Ding-Yuan Tian ²Si-Han Chen ³Wang-Sheng Jin ⁴Yuan Cheng ⁵Jia-Yan Xin ⁶Wei-Wei Li ¹Gui-Hua Zeng ⁴Cheng-Rong Tan ⁴Jie-Ming Jian ⁵Dong-Yu Fan ⁷Jun-Rong Ren ⁵Yu-Hui Liu ⁴Yan-Jiang Wang ⁸Fan Zeng⁴

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作者信息

1. 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
2. Department of Neurology and Center for Clinical Neuroscience,Daping Hospital,Third Military Medical University,Chongqing 400042,China;Department of Cardiology,Southwest Hospital,Third Military Medical University,Chongqing 400042,China
3. Department of Neurology and Center for Clinical Neuroscience,Daping 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
4. Department of Neurology and Center for Clinical Neuroscience,Daping Hospital,Third Military Medical University,Chongqing 400042,China;Chongqing Key Laboratory of Ageing and Brain Diseases,Chongqing 400042,China
5. Department of Neurology and Center for Clinical Neuroscience,Daping Hospital,Third Military Medical University,Chongqing 400042,China
6. Department of Neurology and Center for Clinical Neuroscience,Daping Hospital,Third Military Medical University,Chongqing 400042,China;Department of Clinical Medicine,North Sichuan Medical College,Nanchong 637000,China
7. Department of Neurology and Center for Clinical Neuroscience,Daping Hospital,Third Military Medical University,Chongqing 400042,China;Shigatse Branch,Xinqiao Hospital,Third Military Medical University,Shigatse 857000,China
8. Department of Neurology and Center for Clinical Neuroscience,Daping Hospital,Third Military Medical University,Chongqing 400042,China;The Institute of Brain and Intelligence,Third Military Medical University,Chongqing 400042,China;Chongqing Key Laboratory of Ageing and Brain Diseases,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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Abstract

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.

Key words

Alzheimer's disease/p75 neurotrophin receptor/Extracellular domain/Autoantibody/Amyloid-beta/Immunity

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基金项目

National Natural Science Foundation of China(81870860)

出版年

2023

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

参考文献量33

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