Recognition of tau epitopes by anti-neurofilament antibodies that bind to Alzheimer neurofibrillary tangles.
Recognition of tau epitopes by anti-neurofilament antibodies that bind to Alzheimer neurofibrillary tangles.
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与阿尔茨海默病神经原纤维缠结结合的抗神经丝抗体识别 tau 表位。
DOI：
10.1073/pnas.84.10.3410
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发表时间：
1987
影响因子：
11.1
通讯作者：
Yen,SH
中科院分区：
文献类型：
--
作者：
Ksiezak-Reding,H;Dickson,DW;Davies,P;Yen,SH
研究了11种抗神经丝（抗NF）单克隆抗体与热稳定微管相关蛋白和阿尔茨海默神经元缠结（ANT）的反应性。在NF蛋白的免疫印迹上，抗体识别对大肠杆菌碱性磷酸酶不敏感的表位。八个抗体显示与ANT的反应性，并减少磷酸酶处理后与电印迹NF的结合。相同的八种抗体与来自牛和大鼠脑的tau蛋白反应，与tau蛋白的结合也被磷酸酶显著降低。在与动物tau蛋白结合的八种抗体中，有五种也与正常人脑的tau蛋白结合。所有与动物tau蛋白结合的抗体在冷冻组织切片中染色ANT。在大多数情况下，用胰蛋白酶对组织切片进行简单处理可增强抗体与ANT的结合。所有缺乏与tau蛋白反应性的抗体均不能结合ANT。磷酸酶治疗阿尔茨海默病组织切片没有改变ANT和神经突的免疫反应性与ANT反应性，抗NF抗体的老年斑，除了两个抗体，显示降低结合ANT。相反，轴突染色减少或消除磷酸酶治疗，类似于电印迹NF和tau蛋白的反应。这些结果表明，ANT的抗NF抗体染色可能是由于抗NF与tau蛋白中的表位的交叉反应，轴突，NF和tau中的表位对磷酸酶的作用敏感，而ANT中的大多数表位则不敏感，并且ANT中与NF和tau蛋白共有的一些表位不易与抗体结合。
Eleven anti-neurofilament (anti-NF) monoclonal antibodies were studied for their reactivity with heat-stable, microtubule-associated proteins and Alzheimer neurofibrillary tangles (ANT). On immunoblots of NF proteins, the antibodies recognized epitopes that were variably sensitive to Escherichia coli alkaline phosphatase. Eight of the antibodies showed reactivity with ANT and decreased binding to electroblotted NF after phosphatase treatment. The same eight antibodies reacted with tau proteins from bovine and rat brain, binding to tau proteins was also substantially reduced by phosphatase. Of the eight antibodies that bound to animal tau proteins, five also bound to tau proteins from normal human brain. All of the antibodies that bound to animal tau proteins stained ANT in frozen tissue sections. Brief treatment of tissue sections with trypsin in most cases enhanced antibody binding to ANT. All antibodies that lacked reactivity with tau proteins failed to bind ANT. Phosphatase treatment of Alzheimer tissue sections did not change the immunoreactivity of ANT and neurites in senile plaques with ANT-reactive, anti-NF antibodies, except for two antibodies that showed decreased binding to ANT. In contrast, axonal staining was decreased or eliminated by phosphatase treatment, similar to the response of electroblotted NF and tau proteins. These results suggest that staining of ANT by anti-NF antibodies may be due to cross-reaction of anti-NF with epitopes in tau proteins, the epitopes in axons, NF, and tau are sensitive to the effect of phosphatase, whereas the majority of those in ANT are not, and some of the epitopes in ANT that are shared with NF and tau proteins are not readily accessible to antibody binding.