Regulating factors of PrP 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.


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.
Levavasseur
Etienne
E
INSERM, Avenir Team-Human Prion Diseases, Paris, France.
Laffont-Proust
Isabelle
I
Morain
Emilie
E
Faucheux
Baptiste A
BA
Privat
Nicolas
N
Peoc'h
Katell
K
Sazdovitch
Véronique
V
Brandel
Jean-Philippe
JP
Hauw
Jean-Jacques
JJ
Haïk
Stéphane
S
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
D011328:Prions