title: Regulating factors of PrP glycosylation in Creutzfeldt-Jakob disease--implications for the dissemination and the diagnosis of human prion strains.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: INSERM, Avenir Team-Human Prion Diseases, Paris, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Levavasseur
authors.forename: Isabelle
authors.initials: I
authors.lastname: Laffont-Proust
authors.forename: Emilie
authors.initials: E
authors.lastname: Morain
authors.forename: Baptiste A
authors.initials: BA
authors.lastname: Faucheux
authors.forename: Nicolas
authors.initials: N
authors.lastname: Privat
authors.forename: Katell
authors.initials: K
authors.lastname: Peoc'h
authors.forename: Véronique
authors.initials: V
authors.lastname: Sazdovitch
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Brandel
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Hauw
authors.forename: Stéphane
authors.initials: S
authors.lastname: Haïk
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D007562:Creutzfeldt-Jakob Syndrome / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006031:Glycosylation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011328:Prions / Q000737:chemistry / Q000378:metabolism*; D013788:Thalamus / Q000378:metabolism
chemical_list: D011328:Prions