Australian sporadic CJD analysis supports endogenous determinants of molecular-clinical profiles

Abstract

Objective: To define the protease-resistant prion protein (PrP^res) types and associated clinical profiles in Australian patients with sporadic Creutzfeldt–Jakob disease (CJD) to allow comparison with those reported from other continents and concomitantly reaffirm absence of variant CJD (vCJD).

Methods: Reassessment of available clinical and neuropathologic data on patients referred to the Australian National Creutzfeldt–Jakob Disease Registry (ANCJDR) who died between January 1, 1992, and June 30, 2003, was conducted. Molecular classification of PrP^res was determined by immunoblot analysis of available frozen brain tissue. Brain homogenate pH and codon 129 genotype on the prion protein gene (PRNP) were established.

Results: PrP^res patterns in 35 of 37 patients with sporadic CJD conformed to one of three common reported types. Of a range of clinical features assessed, illness duration was the only clinical feature significantly associated with PrP^res type. Two patients displayed coexistence of more than one PrP type, with one displaying a novel pattern of three PrP^res types in a single brain region. The absence of vCJD was reconfirmed, supported by the lack of the typical PrP^res glycoform pattern.

Conclusions: Given Australia’s geographic isolation and environmental uniqueness, the general congruity of these results with those reported from other continents suggests that endogenous factors predominantly determine sporadic Creutzfeldt–Jakob disease (CJD) phenotypic subtypes or “strains.” These results support a clinicopathologic classification system whereby both PrP^res type and codon 129 genotype are utilized to most accurately depict phenotypic subtypes or strains of sporadic CJD.