| Research Abstract |
During 2 years' support, we established the hydrolytic autoclaving pretreatment to enhance the prion protein (PrP) immunohistochemistry. This pretreatment provided us that abnormal PrP accumulated in the synaptic structures in the central nervous system in patients with Creutzfeldt-Jakob disease (CJD), and in follicular dendritic cells in the lymphoreticular system in CJD-infected mice. To confirm synaptic accumulation of PrP, we examined biochemically and immuno histochemically. Double immunolabelling with anti-PrP and anti-synaptophysin revealed the colocalization of PrP and synaptophysin. In subcellular fractionation, synaptosomal fraction had the highest concentration of abnormal PrP. These results were reported in 1991 and 1992. Next, we did DNA sequencing from various demented persons. We found out novel 5 mutations of PrP gene. These mutations were detected only in CJD or Gerstmann-Straussler syndrome. Among these mutations, we can classify the plaque type or the synaptic type according to the distribution of abnormal PrP accumulation. Patients with synaptic type accumulation have a short clinical course with serious clinical signs, while patients with the plaque type have a long clinical course with slowly progressive dementia. Therefore, the primary structure of PrP directly influences the phenotype of prion diseases. These results were or will be reported in the following references.
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