Comparative study on cerebral amyloids of senile dementia and Creutzfeldt-Jakob disease.

克雅氏病(CJD)和阿尔茨海默病(AD)患者脑内可见淀粉样蛋白沉积。β蛋白是阿尔茨海默病老年斑块的组成部分，普恩蛋白是CJD库鲁斑块的组成部分。我们制备了抗G蛋白或蛋白的抗血清，并能用免疫组织化学方法识别单个大脑淀粉样蛋白沉积。用β蛋白抗血清检测发现，AD患者中枢神经系统中广泛分布有β蛋白。AD患者小脑皮质(100%)、脑干(~100%)和脊髓(33%)均可检出老年斑。Prion蛋白抗血清显示，在21例长期存活的CJD患者中，95%的人大脑中有小的库鲁斑。此外，我们还报道了CJD感染小鼠脑内的库鲁斑是由小鼠Pron蛋白组成，是CJD传播实验中的一个病理标志。在脑淀粉样蛋白的生化方法中，67%的脑死亡在50岁以上，几乎所有60岁以上的脑都可以提取到β蛋白淀粉样蛋白，而在所有CJD患者中都可以检测到Prion蛋白淀粉样蛋白。我们还建立了一种半定量的Western印迹方法。利用这种方法，在中枢神经系统和淋巴网状系统中广泛检测到小鼠Pron蛋白。现在，我们可以检测到0.3毫微克的普恩蛋白。在脑淀粉样蛋白的分子生物学研究中，我们发现了PrP蛋白在开放阅读框中的独特多态。PrP蛋白第102位的脯氨酸到亮氨酸的改变是Gerstmann-Straussler综合征的常见突变。因此，现在可以使用外周血淋巴细胞的DNA来建立诊断。现在，我们将对淀粉样蛋白的形成机制以及AD和CJD的发病机制进行研究。

Cerebral amyloid deposits were seen in the brains of patients with Creutzfeldt-Jakob disease (CJD) and Alzheimer's disease (AD). beta-protein is a component of senile plaques in AD, and prion protein is a component of kuru plaques in CJD. We produced antisera against g-protein or prion protein, and could identify individual cerebral amyloid deposits immunohistochemically. beta-protein antiserum revealed that beta protein is widely distributed in the central nervous system of patients with AD. We could detect senile plaques in cerebellar cortex (100%), brain stem (64-100%), and spinal cord (33%) of patients with AD. Prion protein antiserum revealed that 95% of 21 long survivors with CJD have small kuru plaques in their brains. Additionally, we reported that kuru plaque in the brains of CJD-infected mice is composed of murine prion protein, and is a pathological hallmark in CJD transmission experiment. In biochemical approaches to cerebral amyloids, beta-protein amyloid could be extracted from 67% of brains dead in their 5Os, and from almost all brains over 60s, while prion protein amyloid could be detected in all the patients with CJD. We also established a semi-quantitative Western blot method. Using this method, murine prion protein was widely detected in the central nervous system and the lymphoreticular system. Now, we can detect 0.3 ng of prion protein. In molecular biological approaches to cerebral amyloids, we found out the unique polymorphism in the open reading frame of prion protein. Proline to Leucine change at position 102 of prion protein is a common mutation related to Gerstmann-Straussler syndrome. Therefore, the diagnosis is now established using DNA from peripheral blood lymphocytes. Now, we are going to study mechanisms of amyloid formations and pathogenesis of AD and CJD.