title: Association of prion protein genotype and scrapie prion protein type with cellular prion protein charge isoform profiles in cerebrospinal fluid of humans with sporadic or familial prion diseases.
abstract: The present study investigates whether posttranslational modifications of cellular prion protein (PrP(C)) in the cerebrospinal fluid (CSF) of humans with prion diseases are associated with methionine (M) and/or valine (V) polymorphism at codon 129 of the prion protein gene (PRNP), scrapie prion protein (PrP(Sc)) type in sporadic Creutzfeldt-Jakob disease (sCJD), or PRNP mutations in familial Creutzfeldt-Jakob disease (fCJD/E200K), and fatal familial insomnia (FFI). We performed comparative 2-dimensional immunoblotting of PrP(C) charge isoforms in CSF samples from cohorts of diseased and control donors. Mean levels of total PrP(C) were significantly lower in the CSF from fCJD patients than from those with sCJD or FFI. Of the 12 most abundant PrP(C) isoforms in the examined CSF, one (IF12) was relatively decreased in (1) sCJD with VV (vs. MM or MV) at PRNP codon 129; (2) in sCJD with PrP(Sc) type 2 (vs. PrP(Sc) type 1); and (3) in FFI versus sCJD or fCJD. Furthermore, truncated PrP(C) species were detected in sCJD and control samples without discernible differences. Finally, serine 43 of PrP(C) in the CSF and brain tissue from CJD patients showed more pronounced phosphorylation than in control donors.
authors.affiliation: Department of Neurology, Clinical Dementia Center and DZNE Georg-August University, Göttingen, Germany. Electronic address: matthias.schmitz@med.uni-goettingen.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmitz
authors.affiliation: Department of Neurology, Clinical Dementia Center and DZNE Georg-August University, Göttingen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Lüllmann
authors.affiliation: Department of Neurology, Clinical Dementia Center and DZNE Georg-August University, Göttingen, Germany.
authors.forename: Saima
authors.initials: S
authors.lastname: Zafar
authors.affiliation: Department of Neurology, Clinical Dementia Center and DZNE Georg-August University, Göttingen, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ebert
authors.affiliation: Department of Neurology, Clinical Dementia Center and DZNE Georg-August University, Göttingen, Germany.
authors.forename: Marie
authors.initials: M
authors.lastname: Wohlhage
authors.affiliation: Department of Neurology, Clinical Dementia Center and DZNE Georg-August University, Göttingen, Germany.
authors.forename: Panteleimon
authors.initials: P
authors.lastname: Oikonomou
authors.affiliation: Department of Neurology, Clinical Dementia Center and DZNE Georg-August University, Göttingen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schlomm
authors.affiliation: Slovak Medical University, Bratislava, Slovakia.
authors.forename: Eva
authors.initials: E
authors.lastname: Mitrova
authors.affiliation: Robert Koch-Institute, FG 14 - AG 5: Work Group Unconventional Pathogens and Their Inactivation, Division of Applied Infection Control and Nosocomial Hygiene, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Beekes
authors.affiliation: Department of Neurology, Clinical Dementia Center and DZNE Georg-August University, Göttingen, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Zerr
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003062:Codon; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D015151:Immunoblotting; D034062:Insomnia, Fatal Familial / Q000235:genetics; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D010766:Phosphorylation; D011110:Polymorphism, Genetic; D018621:PrPC Proteins / Q000134:cerebrospinal fluid* / Q000235:genetics*; D018620:PrPSc Proteins / Q000235:genetics*; D017096:Prion Diseases / Q000134:cerebrospinal fluid* / Q000235:genetics*; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics; D020033:Protein Isoforms / Q000134:cerebrospinal fluid / Q000235:genetics; D011499:Protein Processing, Post-Translational; D014633:Valine / Q000235:genetics
chemical_list: D003062:Codon; C512656:PRNP protein, human; D018621:PrPC Proteins; D018620:PrPSc Proteins; D000072002:Prion Proteins; D011328:Prions; D020033:Protein Isoforms; D008715:Methionine; D014633:Valine
keywords: Biomarker; Creutzfeldt-Jakob disease; PrPC charge isoforms; Truncated PrPC forms