Biochemical analysis of abnormal prion protein in the cases with sporadic Creutzfeldt-Jakob disease.

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We could examine one case with sporadic Creutzfeldt-Jakob disease (CJD) in Japan that expressed co-occurrence of type 1 and type 2 protease-resistant prion protein (PrP). Pathological features of the unique case showed both synaptic and perivacuolar PrP depositions. Coexistence of type 1 and type 2 PrP was observed in only single case (4.5%) among 22 cases examined. We have examined PrP types in sporadic CJD cases in United Kingdom and found that 7 (38.9%) out of 18 cases showed coexistence of type 1 and type 2 PrP, which was significantly higher level than in Japan. Genetic differences among races were also elucidated as reported previously ; codon 129 polymorphism of the prion protein gene consisted entirely of methionin homozygosity in all Japanese cases (100%), in contrast with UK cases (55.6%). Although the pathological grade of pontine nuclei varied among cases, the severity was not affected by the difference of pathogen strain, but merely by the time course of disease progression. Homogeneity of PrP types and clinicopathological features in Japanese sporadic CJD cases may be based on the ethnic background in part.Because the biochemical properties of protease-resistant PrP in Japanese sporadic CJD cases were relatively homogeneous, we tried to detect PrP oligomers so that we could classify the abnormal PrP based on the conformational differences. We determined an alternative method, which would be a simple and riskless procedure to detect PrP aggregates. The optimized condition was established to solubilize cellular PrP as monomers and leave abnormal PrP as aggregates or oligomers. Therefore we could separate PrP aggregates by the simple method in a shorter time. Recently it has been found that PrP oligomers rather than highly aggregated PrP fibrils have more potent infectivity and neurotoxicity. This simple method for PrP oligomer detection may be suitable for practical use for the analysis of prion diseases.