As the aetiology of sporadic CJD suggests involvement of a stochastic process such as somatic PRNP mutation (Brown et al. 1987; Collinge 2001; Wadsworth et al. 2006; Mead et al. 2007), it seems probable that part of the phenotypic and neuropathological heterogeneity seen in sporadic CJD may be related to peripheral versus central initiation of prion replication. This evidence concerns the gene PRNP and sporadic Creutzfeldt-Jakob disease.