Bancher C, Grundke-Iqbal I, Iqbal K, Fried V A, Smith H T, Wisniewski H M
New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
Brain Res. 1991 Jan 18;539(1):11-8. doi: 10.1016/0006-8993(91)90681-k.
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.
在阿尔茨海默病大脑的组织切片上，4种针对tau蛋白的抗体不仅能免疫标记神经原纤维缠结、神经炎性斑块和神经毡丝，还能标记海马体和皮质神经元亚群中无缠结的细胞质，我们认为这些神经元正处于形成双螺旋丝（PHF）之前的改变阶段。用碱性磷酸酶对组织切片进行预处理，会导致针对tau分子氨基末端和中间区域的抗体染色强度增加以及免疫反应性病变数量增多。使用7种识别泛素的单克隆抗体中的任何一种，均未观察到弥漫性神经元染色。我们得出结论：（1）tau蛋白异常磷酸化发生在其并入PHF之前，并导致其在神经细胞体中积累；（2）仅当神经原纤维缠结已经形成时，才能观察到泛素与之相关。
