RECOGNITION OF ALZHEIMER PAIRED HELICAL FILAMENTS BY MONOCLONAL NEUROFILAMENT ANTIBODIES IS DUE TO CROSSREACTION WITH TAU-PROTEIN
RECOGNITION OF ALZHEIMER PAIRED HELICAL FILAMENTS BY MONOCLONAL NEUROFILAMENT ANTIBODIES IS DUE TO CROSSREACTION WITH TAU-PROTEIN
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DOI：
10.1073/pnas.84.10.3415
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发表时间：
1987-05-01
影响因子：
11.1
通讯作者：
SELKOE, DJ
中科院分区：
文献类型：
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作者：
NUKINA, N;KOSIK, KS;SELKOE, DJ
神经元缠结和老年斑是阿尔茨海默病的主要病理特征。神经纤维缠结和老年斑的神经突含有成对的螺旋丝（PHF），其由两个10 nm的丝扭曲成双螺旋组成。PHF的前体蛋白尚不完全清楚。为了识别这些前体，在过去十年中进行了许多免疫化学研究。有两个明显矛盾的结果被报道。(i)一些，但不是全部，单克隆抗体染色神经纤维缠结。(ii)多克隆抗体制备PHF纯化NaDodSO4，因为他们不寻常的不溶性不承认正常的蛋白质，包括神经丝，电泳转移印迹的人脑匀浆。这些结果已经在几个实验室中得到证实，包括使用电子显微镜标记。最近，我们报道了多克隆PHF抗体包括tau蛋白抗体，一个家庭的热稳定微管相关磷蛋白，和tau抗体染色阿尔茨海默氏症神经元缠结。据报道，识别缠结的那些单克隆神经丝抗体针对磷酸化表位。这些事实促使我们重新检查某些染色神经纤维缠结的神经丝单克隆抗体。我们检查的所有染色缠结的单克隆神经丝抗体，包括最初报道的那些，都与tau蛋白反应。我们的研究结果表明，这些抗体与PHF中的磷酸化tau蛋白反应，而不是神经丝蛋白，突出了在免疫化学研究中使用磷酸化蛋白表位抗体的问题。现在需要在人类成对螺旋丝中存在神经丝蛋白的独立证据。
Neurofibrillary tangles and senile plaques are the principal pathological features of Alzheimer disease. Neurofibrillary tangles and the neurites of senile plaques contain paired helical filaments (PHF) that consist of two 10-nm filaments twisted into a double helix. The precursor proteins of PHF are not fully known. To identify these precursors, numerous immunochemical studies have been carried out during the past decade. Two apparently conflicting results have been reported. (i) Some, but not all, monoclonal antibodies to neurofilaments stained neurofibrillary tangle. (ii) Polyclonal antibodies prepared to PHF purified in NaDodSO4 because of their unusual insolubility did not recognize normal proteins, including neurofilaments, on electrophoretic transfer blots of human brain homogenates. These results have been confirmed in several laboratories, including by the use of electron microscopic labeling. Recently, we reported that polyclonal PHF antibodies include antibodies to tau proteins, a family of heat-stable microtubule-associated phosphoproteins, and that antibodies to tau stain Alzheimer neurofibrillary tangles. Those monoclonal neurofilament antibodies that recognize tangles are reported to be directed against phosphorylated epitopes. These facts prompted us to reexamine certain neurofilament monoclonal antibodies that stain neurofibrillary tangles. All monoclonal neurofilament antibodies that stain tangles that we examined, including those initially reported, reacted with tau proteins. Our results suggest that these antibodies react with phosphorylated tau proteins in PHF, not neurofilament proteins, highlighting the problem of using antibodies to phosphorylated protein epitopes in immunochemical studies. Independent evidence for the presence of neurofilament proteins in human paired helical filaments is now required.