Immunohistochemical studies of the PrP(CJD) deposition in Creutzfeldt-Jakob disease.

The PrP(CJD) deposition in eight brains of sporadic Creutzfeldt-Jakob disease (CJD) was examined immunohistochemically using both hydrolytic autoclaving and formic acid pretreatment in order to understand the pathogenesis of CJD. Synaptic-type PrP immunoreactivity was revealed in the gray matter in all cases and had a tendency to be weaker in devastated areas in cases with a longer duration of illness. However, in one particular case with numerous prion plaques, the degeneration was relatively mild while PrP(CJD) immunoreactivity was intense despite the longest duration of illness among the examined cases. Deep layer accentuation of PrP(CJD) immunoreactivity was observed in the cerebral cortices in most cases. This staining pattern, however, disappeared in a burnt-out lesion exhibiting status spongiosus. The granular layer was damaged mostly in the cerebellum of the advanced cases. PrP(CJD) and synaptophysin immunoreactivities decreased as the tissue degeneration progressed. Interestingly, the Purkinje cells had no positivity for PrP(CJD) in all cases, although the neurons in relatively preserved cerebellum showed apparent positivity for synaptophysin. In the Ammon's horn and subiculum the neurons were well preserved despite the marked immunoreactivity for PrP(CJD) in all cases, although some cases demonstrated severe spongiform change. Approximately half of the cases showed intracytoplasmic inclusion body-like immunoreactivity for PrP(CJD) in neurons of the dentate nucleus. These findings suggest that PrP(CJD) deposition may be an event that precedes neuronal degeneration evolving from deeper layers of the cerebral cortex. Although the Ammon's horn and subiculum showed striking PrP(CJD) deposition and spongiform change, neuronal loss did not take place, suggesting that deposited PrP(CJD) itself seems not to be directly harmful to the neurons. Some investigators have assumed that microglia activated by PrP(CJD) plays an important role in neuronal degeneration. Considering this, we speculate that microglia in the Ammon's horn and subiculum may have a unique characteristic of not responding to PrP(CJD).