PRION PROTEIN GENOTYPE AND PATHOLOGICAL PHENOTYPE STUDIES IN SPORADICCREUTZFELDT-JAKOB-DISEASE

A comparative semi-automated morphometric study was performed on the d istribution of prion protein, spongiform change and astrocytosis in th e brains of nine cases of sporadic Creutzfeldt-Jakob disease of differ ing genotype at the methionine-valine polymorphism at codon 129 of the prion protein gene. Custom-designed image analysis software was used to produce objective figures for each of the different pathological fe atures throughout 13 different areas of the brain used for analysis. A significant positive correlation was observed between prion protein d eposition and astrocytosis in all cases and no significant correlation was observed between spongiform change and prion protein deposition. Different patterns of pathology were found to relate to codon 129 geno type; valine homozygosity favoured the targeting of pathology to deep grey matter structures, while methionine homozygosity favoured cortica l targeting of pathology. These results provide evidence that prion pr otein deposition is closely associated with an astrocytic reaction and suggest that codon 129 genotype may influence the pathological phenot ype.