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

在克雅氏病（CJD）和阿尔茨海默病（AD）患者的大脑中可见脑淀粉样蛋白沉积。β蛋白是AD老年斑的组成部分，朊蛋白是CJD库鲁斑块的组成部分。我们制备了抗g蛋白或朊蛋白的血清，并能通过免疫组织化学方法识别个体脑淀粉样蛋白沉积。β蛋白抗血清显示β蛋白广泛分布于AD患者的中枢神经系统。我们可以在AD患者的小脑皮层（100%）、脑干（64-100%）和脊髓（33%）检测到老年斑。朊蛋白抗血清显示，21名长期存活的克雅氏病患者中，95%的人大脑中有小的库鲁菌斑块。此外，我们报道了CJD感染小鼠大脑中的库鲁斑块由小鼠朊蛋白组成，是CJD传播实验的病理标志。在大脑淀粉样蛋白的生化方法中，可以从67%的50多岁死亡的大脑中提取-蛋白淀粉样蛋白，从几乎所有60多岁以上的大脑中提取-蛋白淀粉样蛋白，而在所有CJD患者中都可以检测到朊蛋白淀粉样蛋白。我们还建立了半定量Western blot方法。该方法在小鼠中枢神经系统和淋巴网状系统中广泛检测到朊病毒蛋白。现在，我们可以检测到0.3 ng的朊病毒蛋白。在脑淀粉样蛋白的分子生物学研究中，我们发现了朊蛋白开放阅读框中独特的多态性。朊蛋白102位脯氨酸向亮氨酸转变是Gerstmann-Straussler综合征的常见突变。因此，目前的诊断方法是利用外周血淋巴细胞的DNA。现在，我们将研究淀粉样蛋白的形成机制和AD和CJD的发病机制。

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.