Trojanowski J Q, Schuck T, Schmidt M L, Lee V M
Department of Pathology and Laboratory Medicine (Neuropathology), University of Pennsylvania School of Medicine, Philadelphia 19104-6079.
J Histochem Cytochem. 1989 Feb;37(2):209-15. doi: 10.1177/37.2.2492045.
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 tau 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 less than 24 hr did not affect the distribution of tau, but the method used to denature tissues did, i.e., microwave treatment preserved tau 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, microenvironmental factors in different neuroanatomical sites may affect the regional expression of tau.
在人类大脑中，针对tau蛋白的抗体主要标记异常结构而非正常结构。这可能反映了由于死后蛋白水解、疾病或物种差异导致的免疫反应性改变。我们通过使用针对牛和人类tau中与磷酸无关的表位的新型单克隆抗体（MAb），比较牛和人类死后神经系统组织以及人类神经细胞系中tau的分布，来解决这个问题。在新皮层、海马体和小脑中，免疫反应性tau广泛表达，但定位于神经元的轴突-神经毡区域。在脊髓和周围神经系统中，tau免疫反应性同样定位于特定区域，但含量较少。在表达神经丝或胶质丝蛋白的胶质细胞或人类神经细胞系中，我们的MAb未检测到免疫反应性tau。组织变性的死后延迟时间少于24小时不会影响tau的分布，但用于使组织变性的方法会产生影响，即微波处理比诸如Bouin氏液等化学固定剂更有效地保留tau免疫反应性，并且福尔马林固定的组织样本与我们的抗tau MAb反应较差。我们得出结论，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，并且人类组织中正常免疫反应性tau的可视化关键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会影响tau的区域表达。
