Abnormal isoform of prion proteins accumulates in the synaptic structures of the central nervous system in patients with Creutzfeldt-Jakob disease.

A new method, which enabled the first immunohistochemical documentation of abnormal prion protein (PrP) in all patients with Creutzfeldt-Jakob disease (CJD), was established. This method designated as "hydrolytic autoclaving" revealed punctate PrPCJD stainings around the neuronal cell bodies and dendrites in CJD brains. These punctate stainings were almost identical with that of synaptophysin, suggesting PrPCJD accumulations in the synaptic structures. Subcellular fractionation revealed that prion protein in Creutzfeldt-Jakob disease (PrPCJD) was most concentrated in the synaptosomal fraction. In CJD patients with a long clinical course, synaptophysin immunoreactivity decreased, and synaptic PrPCJD accumulated with a wider distribution. These results suggest that synaptic PrPCJD accumulations might be responsible for the neuronal dysfunction and degeneration in CJD.