| Research Abstract |
Creutzfeldt-Jakob disease (CJD) is a intractable disease of central nervous system, causing transmissible dementia in human. The pathogen of CJD remains unknown, however, the prion hypothesis have been declared in scrapie infections.
I investigated the prion hypothesis in CJD. The purification protocols of prion yield amyloid proteins from CJD brains and non-transmissible amyloidosis. The amyloid fibril protein of CJD is composed of specific protein (prion protein), which is different from other amyloid proteins. Immunohistochemically, anti-prion protein reacted positively with kuru plaques in CJD brains, but not with other amyloid deposits. In addition, we reported that Congophilia of kuru plaque is modified by inactivation procedures on CJD agents. As the second step, we produced the antisera against human prion, mouse prion, and prion protein synthetic peptides. These antisera and a newly developed formic acid pretreatment revealed the very small kuru plaques in human and mouse CJD brain sections. In human CJD, almost all patients with long clinical couse (over 1 year) have kuru plaques in their brains. In mouse CJD, the kuru plaques are composed of mouse prion proteins, but not of human prion proteins. Therefore, kuru plaques can be one of the pathological hallmarks in CJD. The diagnosis of CJD is easily confirmed by the Western blotting technique using antiprion proteins. Prion protein can be detected in 5 mg (wet weight) of brain tissues, and 25 to 50 mg of spleen tissues from CJD-infected mice. In order to increase the sensitivity of the prion protein detection, we are going to establish the radioimmunoassay using our antisera.
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