Endoh R, Ogawara M, Iwatsubo T, Nakano I, Mori H
Department of Neuropathology, University of Tokyo School of Medicine, Japan.
Brain Res. 1993 Jan 22;601(1-2):164-72. doi: 10.1016/0006-8993(93)91707-y.
Using seven independent antibodies against the amino terminal to the carboxyl terminal sequence of tau, we biochemically analyzed and compared the neuropathogenesis of two Alzheimer's disease brains from the viewpoint of abnormal processing on tau, the major constituent of paired helical filaments. One showed typical Alzheimer's disease with senile plaques and intracellular neurofibrillary tangles. The other showed advanced Alzheimer's disease with senile plaques and virtually the sole of ghost tangles without intracellular neurofibrillary tangles. We confirmed the previous observation that the carboxyl thirds of tau are tightly associated with paired helical filaments isolated in the presence of SDS. We found that biochemically, ghost tangles were abnormally phosphorylated and lacked the final carboxyl terminal sequence as well as the amino half of tau, unlike intracellular tangles. From these biochemical results taken together with the current evidence for ubiquitin in ghost tangles, we concluded that ghost tangles were extensively processed and irreversibly transformed into highly insoluble extracellular deposits.
我们使用了七种针对tau蛋白从氨基末端到羧基末端序列的独立抗体，从tau蛋白（成对螺旋丝的主要成分）异常加工的角度，对两个阿尔茨海默病大脑的神经病理发生过程进行了生化分析和比较。其中一个呈现出伴有老年斑和细胞内神经原纤维缠结的典型阿尔茨海默病。另一个则呈现出伴有老年斑且几乎只有空泡缠结而无细胞内神经原纤维缠结的晚期阿尔茨海默病。我们证实了之前的观察结果，即在SDS存在的情况下，tau蛋白的羧基端三分之一与分离出的成对螺旋丝紧密相关。我们发现，从生化角度来看，与细胞内缠结不同，空泡缠结存在异常磷酸化，并且缺少tau蛋白的最终羧基末端序列以及氨基端一半的序列。综合这些生化结果以及目前关于空泡缠结中泛素的证据，我们得出结论，空泡缠结经过了广泛加工，并不可逆地转化为高度不溶性的细胞外沉积物。
