ABNORMAL PHOSPHORYLATION OF TAU-PRECEDES UBIQUITINATION IN NEUROFIBRILLARY PATHOLOGY OF ALZHEIMER-DISEASE
ABNORMAL PHOSPHORYLATION OF TAU-PRECEDES UBIQUITINATION IN NEUROFIBRILLARY PATHOLOGY OF ALZHEIMER-DISEASE
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DOI：
10.1016/0006-8993(91)90681-k
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发表时间：
1991-01-18
期刊：
影响因子：
2.9
通讯作者：
WISNIEWSKI, HM
中科院分区：
文献类型：
--
作者：
BANCHER, C;GRUNDKEIQBAL, I;WISNIEWSKI, HM
在阿尔茨海默氏症大脑的组织切片上，tau蛋白的4种抗体不仅标记了神经元缠结、神经炎斑和神经纤维丝，而且还标记了海马和皮质神经元的一个子集的无缠结细胞质，我们认为这是在成对螺旋丝（PHF）形成之前的改变阶段。用碱性磷酸酶预处理组织切片导致染色强度和免疫反应性病变的数量增加，其中抗体针对氨基末端和tau分子的中间区域。7种识别泛素的单克隆抗体均未观察到弥漫性神经元染色。我们得出结论：（1）tau蛋白的异常磷酸化发生在其掺入PHF之前，并导致其在神经细胞体中的积累;（2）泛素仅在神经元缠结已经形成时才被发现相关。
On tissue sections of Alzheimer brain, 4 antibodies to tau immunolabel not only neurofibrillary tangles, neuritic plaques and neuropil threads but also the tangle-free cytoplasm of a subset of hippocampal and cortical neurons we believe to be at a stage of alteration preceding the formation of paired helical filaments (PHF). Pretreatment of tissue sections with alkaline phosphatase leads to an increase in staining intensity and in number of immunoreactive lesions with antibodies directed to an amino terminal and to a mid-region of the tau molecule. The diffuse neuronal staining could not be observed with any of 7 monoclonal antibodies recognizing ubiquitin. We conclude (1) that abnormal phosphorylation of tau occurs prior to its incorporation into PHF and leads to its accumulation in the nerve cell body and (2) that ubiquitin is seen associated only when a neurofibrillary tangle is already formed.