| Research Abstract |
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.
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