The cellular
prion protein (PrP(c)) is a multifunctional, highly conserved and ubiquitously expressed
protein. It undergoes a number of modifications during its post-translational processing, resulting in different PrP(c) glycoforms and truncated PrP(c) fragments. Limited data are available in humans on the expression and cleavage of PrP(c). In this study we investigated the PrP(c)
isoform composition in the cerebrospinal fluid from patients with different human
prion diseases. The first group of patients was affected by
sporadic Creutzfeldt-Jakob disease exhibiting different PrP
codon 129 genotypes. The second group contained patients with a genetic form of
Creutzfeldt-Jakob disease (E200K). The third group consisted of patients with
fatal familial insomnia and the last group comprised cases with the Gerstmann-Sträussler-Scheinker syndrome. We examined whether the PrP
codon 129 polymorphism in
sporadic Creutzfeldt-Jakob disease as well as the type of
prion disease in human patients has an impact on the glycosylation and processing of PrP(c). Immunoblotting analyses using different monoclonal PrP(c)
antibodies directed against various
epitopes of PrP(c) revealed, for all examined groups of patients, a consistent predominance of the glycosylated PrP(c)
isoforms as compared with the unglycosylated form. In addition, the antibody SAF70 recognized a variety of PrP(c) fragments with sizes of 21, 18, 13 and 12 kDa. Our findings indicate that the polymorphisms at PrP
codon 129, the E200K mutation at
codon 200 or the examined types of human
transmissible spongiform encephalopathies do not exert a measurable effect on the glycosylation and processing of PrP(c) in human
prion diseases.