The diversities of PrP(Sc) distributions and pathologic changes in various brain regions from a Chinese patient with G114V genetic CJD.

Human genetic Creutzfeldt-Jakob disease (gCJD; one of the prion diseases) is caused by point mutations and insertions in the prion protein gene (PRNP). Previously we have reported a Chinese gCJD case with a substitution of valine (V) for glycine (G) at codon 114. To investigate the detailed pathogenic and pathologic characteristics of G114V gCJD, 10 different brain regions were thoroughly analyzed. PrP-specific Western blots and immunohistochemical (IHC) assays identified larger amounts of PrP(Sc) in the regions of brain cortex. Assays of the transcriptions of PrP-specific mRNA by RT-PCR and real-time PCR showed comparable levels in 10 brain regions. In line with the distribution of PrP(Sc) , typical vacuolations in brains, markedly in four cortex regions, were detected. Contrast to the distributing features of spongiform and of PrP(Sc) , massive gliosis was detected in all brain regions by GFAP-specific IHC tests. Moreover, two-dimensional gel immunoblots found three major sets of PrP(Sc) spots, indicating that PrP(Sc) in brain tissues was a mixture of molecules with different biochemical properties. The data here provide the pathogenic and neuropathological features of G114V gCJD.