DISTRIBUTION OF TAU PROTEINS IN THE NORMAL HUMAN CENTRAL AND PERIPHERAL NERVOUS-SYSTEM
DISTRIBUTION OF TAU PROTEINS IN THE NORMAL HUMAN CENTRAL AND PERIPHERAL NERVOUS-SYSTEM
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DOI：
10.1177/37.2.2492045
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发表时间：
1989-02-01
影响因子：
3.2
通讯作者：
LEE, VMY
中科院分区：
文献类型：
--
作者：
TROJANOWSKI, JQ;SCHUCK, T;LEE, VMY
在人脑中，tau 蛋白抗体主要标记异常结构而不是正常结构。这可能反映了由于死后蛋白水解、疾病或物种差异而导致的免疫反应性改变。我们通过使用特异针对牛和人 tau 磷酸独立表位的新型单克隆抗体 (MAb)，比较 tau 在牛和人死后神经系统组织以及人神经细胞系中的分布，解决了这个问题。在新皮质、海马和小脑中，免疫反应性 tau 蛋白广泛表达，但分离到神经元的轴突-神经纤维域中。在脊髓和周围神经系统中，tau 免疫反应性也有类似的分离，但数量较少。我们的 MAb 在神经胶质细胞或表达神经丝或神经胶质丝蛋白的人神经细胞系中未检测到免疫反应性 tay。死后组织变性延迟< 24小时不会影响tau蛋白的分布，但用于使组织变性的方法确实会影响tau蛋白的分布，即微波处理比布安溶液等化学固定剂更有效地保留了tau蛋白的免疫反应性，而福尔马林固定的组织样本与我们的抗tau蛋白单克隆抗体反应较差。我们得出的结论是，tau 蛋白在人类神经系统中的分布与灌注固定实验动物中描述的分布相似，并且人体组织中正常免疫反应性 tau 蛋白的可视化很大程度上取决于用于使死后组织样本变性的程序。此外，不同神经解剖部位的微环境因素可能影响tau的区域表达。
In human brain, antibodies to tau proteins primarily label abnormal rather than normal structures. This might reflect altered immunoreactivity owing to post-mortem proteolysis, disease, or species differences. We addressed this issue by comparing the distribution of tau in bovine and human post-mortem nervous system tissues and in human neural cell lines, using new monoclonal antibodies (MAb) specific for phosphate-independent epitopes in bovine and human tau. In neocortex, hippocampus, and cerebellum, immunoreactive tau was widely expressed but segregated into the axon-neuropil domain of neurons. In spinal cord and peripheral nervous system, tau immunoreactivity was similarly segregated but less abundant. No immunoreactive tay was detected with our MAb in glial cells or in human neural cell lines that express neurofilament or glial filament proteins. Post-mortem delays in tissue denaturation of < 24 hr did not affect the distribution of tau, but the method used to denature tissues did, i.e., microwave treatment preserved tay immunoreactivity more effectively than chemical fixatives such as Bouin''s solution, and formalin-fixed tissue samples reacted poorly with our anti-tau MAb. We conclude that the distribution of tau proteins in human nervous system is similar to that described in perfusion-fixed experimental animals, and that visualization of normal immunoreactive tau in human tissues is critically dependent on the procedures used to denature post-mortem tissue samples. Furthermore, micro-environmental factors in different neuroanatomical sites may affect the regional expression of tau.