Regulating Factors of PrPres Glycosylation in Creutzfeldt-Jakob Disease - Implications for the Dissemination and the Diagnosis of Human Prion Strains

Objective The glycoprofile of pathological prion protein (PrP res ) is widely used as a diagnosis marker in Creutzfeldt-Jakob disease (CJD) and is thought to vary in a strain-specific manner. However, that the same glycoprofile of PrP res always accumulates in the whole brain of one individual has been questioned. We aimed to determine whether and how PrP res glycosylation is regulated in the brain of patients with sporadic and variant Creutzfeldt-Jakob disease. Methods PrP res glycoprofiles in four brain regions from 134 patients with sporadic or variant CJD were analyzed as a function of the genotype at codon 129 of PRNP and the Western blot type of PrP res . Results The regional distribution of PrP res glycoforms within one individual was heterogeneous in sporadic but not in variant CJD. PrP res glycoforms ratio significantly correlated with the genotype at codon 129 of the prion protein gene and the Western blot type of PrP res in a region-specific manner. In some cases of sCJD, the glycoprofile of thalamic PrP res was undistinguishable from that observed in variant CJD. Interpretation Regulations leading to variations of PrP res pattern between brain regions in sCJD patients, involving host genotype and Western blot type of PrP res may contribute to the specific brain targeting of prion strains and have direct implications for the diagnosis of the different forms of CJD.