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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针对 p75NTR 胞外结构域的天然自身抗体水平升高会加剧阿尔茨海默氏病的病理学
DOI：
10.1007/s12264-022-00936-4
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发表时间：
2022-08
影响因子：
5.6
通讯作者：
Fan Zeng
中科院分区：
文献类型：
--
作者：
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
p75神经营养因子受体（p75 NTR）胞外区（p75 ECD）拮抗Aβ神经毒性并促进Aβ清除阿尔茨海默病（AD）。p75 ECD脱落受损是AD的一个重要病理过程，但其调控机制尚不清楚。本研究旨在探讨AD患者中天然存在的抗p75 ECD自身抗体（p75 ECD-NAbs）的存在和变化及其对AD病理学的影响。我们发现AD患者脑脊液中p75 ECD-NAbs的水平升高，并与脑脊液中p75 ECD的水平呈负相关。p75 ECD主动免疫的转基因AD小鼠显示出较低的p75 ECD水平和更严重的AD病理学，以及更差的认知功能比对照组，分别用Re-p75 ECD（p75 ECD的反向序列）和磷酸盐缓冲盐水免疫。这些发现证明了p75 ECD-NAb对p75 NTR/p75 ECD失衡的影响，为自身免疫和p75 NTR在AD中的作用提供了新的见解。
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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影响因子：
13.6
作者：
Liu YH;Wang J;Li QX;Fowler CJ;Zeng F;Deng J;Xu ZQ;Zhou HD;Doecke JD;Villemagne VL;Lim YY;Masters CL;Wang YJ
通讯作者：
Wang YJ
影响因子：
4.7
作者：
Wang, Qing-Hua;Wang, Ye-Ran;Wang, Yan-Jiang
通讯作者：
Wang, Yan-Jiang
影响因子：
2.9
作者：
Levin, Eli C.;Acharya, Nimish K.;Nagele, Robert G.
通讯作者：
Nagele, Robert G.
影响因子：
14.5
作者：
Rawji, Khalil S.;Mishra, Manoj K.;Yong, V. Wee
通讯作者：
Yong, V. Wee
影响因子：
5.8
作者：
Fan Zeng;Jian-Jun Lu;Xin-Fu Zhou;Yanjiang Wang
通讯作者：
Fan Zeng;Jian-Jun Lu;Xin-Fu Zhou;Yanjiang Wang