ABNORMAL PHOSPHORYLATION OF THE MICROTUBULE-ASSOCIATED PROTEIN-TAU (TAU) IN ALZHEIMER CYTOSKELETAL PATHOLOGY
ABNORMAL PHOSPHORYLATION OF THE MICROTUBULE-ASSOCIATED PROTEIN-TAU (TAU) IN ALZHEIMER CYTOSKELETAL PATHOLOGY
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DOI：
10.1073/pnas.83.13.4913
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发表时间：
1986-07-01
影响因子：
11.1
通讯作者：
BINDER, LI
中科院分区：
文献类型：
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作者：
GRUNDKEIQBAL, I;IQBAL, K;BINDER, LI
微管相关蛋白tau的单克隆抗体。（tau）标记了阿尔茨海默病大脑中成对螺旋丝（PHF）的两个主要位置——神经原纤维缠结和斑块神经突。该抗体还标记了用NaDodSO4反复洗涤的分离的PHF。在免疫标记之前，用碱性磷酸酶对组织切片进行去磷酸化，显著增加了抗体识别的缠结和斑块的数量。在去磷酸化或非去磷酸化的组织切片中，斑块核心淀粉样蛋白未被染色。在免疫印迹上，PHF多肽只有在去磷酸化时才容易被标记。相比之下，一种市售的针对神经丝磷酸化表位的单克隆抗体标记了组织中的缠结和斑块神经突起，但在免疫印迹上没有标记任何PHF多肽。PHF多肽用。tau单克隆抗体标记。，用分离的PHF抗体识别的多肽进行电泳。tau的抗体。-标记的微管来自正常人脑，在体外组装，但同样处理的阿尔茨海默氏症大脑制剂必须去磷酸化，才能完全被这种抗体识别。这些发现表明。tau。是一种异常磷酸化的PHF蛋白成分。
A monoclonal antibody to the microtubule-associated protein .tau. (tau) labeled some neurofibrillary tangles and plaque neurites, the two major locations of paired-helical filaments (PHF), in Alzheimer disease brain. The antibody also labeled isolated PHF that had been repeatedly washed with NaDodSO4. Dephosphorylation of the tissue sections with alkaline phosphatase prior to immunolabeling dramatically increased the number of tangles and plaques recognized by the antibody. The plaque core amyloid was not stained in either dephosphorylated or nondephosphorylated tissue sections. On immunoblots PHF polypeptides were labeled readily only when dephosphorylated. In contrast, a commercially available monoclonal antibody to a phosphorylated epitope of neurofilaments that labeled the tangles and the plaque neurites in tissue did not label any PHF polypeptides on immunoblots. The PHF polypeptides, labeled with the monoclonal antibody to .tau., electrophoresed with those polypeptides recognized by antibodies to isolated PHF. The antibody to .tau.-labeled microtubules from normal human brains assembled in vitro but identically treated Alzheimer brain preparations had to be dephosphorylated to be completely recognized by this antibody. These findings suggest that .tau. in Alzheimer brain is an abnormally phosphorylated protein component of PHF.