阿尔茨海默病患者脑内p75神经营养因子受体(p75NTR)的表达及与老年斑位置关系的研究  

Expression profile of p75NTR and its relationship with formation of amyloid plaques in the brain of Alzheimer's disease patients

作　　者：王叶冉[1] 刘雨辉 梁春荣[1] 曾凡[1] 卜先乐 矫树生[1] 王庆华[1] 姚秀卿[1] 周华东[1] 王延江[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所神经内科,重庆400042

出　　处：《解放军医学杂志》2014年第5期379-382,共4页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金(30973144;81270423);重庆市杰出青年科学基金(CSTC 2010BA5004);中国博士后科学基金(2013T60955);重庆市博士后科研项目(Xm201342)~~

摘　　要：目的探讨阿尔茨海默病(AD)患者脑内p75神经营养因子受体(p75NTR)的表达状况及其与老年斑的空间位置关系。方法分别采用AD患者与认知正常对照者(各4例)海马组织、12月龄雄性AD转基因小鼠(APPswe/PS1dE9)与同窝雄性野生型小鼠(各10只)脑组织,通过免疫组织化学法观察p75NTR在人与小鼠海马神经元及神经纤维中的表达及与老年斑的空间位置关系,Western blotting检测AD患者及转基因小鼠脑内p75NTR的表达水平。结果 AD患者和认知正常对照者海马神经元胞体和神经纤维均表达p75NTR,APPswe/PS1dE9小鼠神经纤维表达p75NTR,而野生型小鼠神经纤维内未见p75NTR表达,APPswe/PS1dE9和野生型小鼠海马神经元内均未见明显p75NTR表达。在AD患者和APPswe/PS1dE9小鼠海马内可见p75NTR阳性的变性神经末梢,该神经纤维末梢主要分布于老年斑的中心部位。Western blotting检测显示,AD患者和APPswe/PS1dE9小鼠脑组织p75NTR的表达水平分别显著高于认知正常者和野生型小鼠。结论 p75NTR在AD患者脑内表达增加,并且可能参与了老年斑的形成。Objective To explore the expression and distribution of p75 neurotrophin receptor （p75NTR） in brains of patients with Alzheimer＇s disease （AD） and its spatial relationship with amyloid plaques. Methods Mouse brain tissues from transgenic mice B6C3-Tg （APPswe/PS1dE9） and their wild type littermates （n=10）, and human brain tissues from AD patients and age-matched healthy individuals （n=4） were collected. Expression and distribution of p75NTR in brains of human and mice were detected by Immunohistochemistry, and the levels of p75NTR in brains were quantified by Western-blotting. Results The p75NTR expression was observed on neurofibrils of AD patients, transgenic mice and cognitive normal controls, but no on wild type mice; p75NTR expression was observed in neurons of human but not mice. The p75NTR immunoreactivity was mainly located in the center of amyloid plaques distributed in hippocampus and cortex of AD patients and transgenic mice. Western blotting results demonstrated that the levels of p75NTR in brains of AD patients and transgenic mice were significantly higher than controls. Conclusion p75NTR expression is up-regulated in hippocampus and cortex of AD patients, may participate in the formation of amyloid plaques.

关 键 词：阿尔茨海默病 受体 神经生长因子 淀粉样Β蛋白 

分 类 号：R749.16[医药卫生—神经病学与精神病学]