Neuropathological study of cerebellar degeneration in prion disease.

In order to clarify the relationship between cerebellar degeneration and prion protein (PrP) accumulation, 17 cases of sporadic Creutzfeldt-Jakob disease (CJD) and three cases of Gerstmann-Sträussler syndrome (GSS) were analyzed neuropathologically. Immunohistochemical staining for PrP showed synaptic-type deposits in all of the CJD cases. The punctate PrP stains in CJD patients were almost identical with those of synaptophysin, suggesting that PrP had accumulated in the synaptic structures. Synapses damage due to PrP accumulation seemed to develop prior to granule cell loss. PrP accumulation was inversely correlated with granule cell loss. The degree of atrophy in the molecular layer was compatible with granule cell loss. The nodulus showed severe PrP accumulation when compared with other sites in the cerebellum. How-ever, in GSS cases, the loss of Purkinje cells and dentate nucleus neurons was obvious. Further, immunohisto-chemical staining for PrP demonstrated Kuru plaque-type and synaptic-type depositions in the molecular layer, the granular cell layer, and the dentate nucleus, which was different from CJD cases.