Creutzfeldt-Jakob disease is a transmissible spongiform encephalopathy characterized clinically by dementia, myoclonus and, in some cases, periodic triphasic EEG-patterns. Neuropathologically the main features are spongiform change, astrocytosis, neuronal cell loss and, in a small percent of cases, amyloid plaques. Prion protein immunohistochemistry is used for definitive diagnosis of these diseases. In our study we present different immunostaining patterns in light microscopy using anti prion protein, and with immunogold labelling for ultrastructural localization of prion protein. Our results demonstrate the clinicopathological heterogeneity of Creutzfeldt-Jakob disease and reveal the role of the endosomal-lysosomal system in the pathogenesis.