• Matthias Schmitz, Katharina Lüllmann, Saima Zafar, Elisabeth Ebert, Marie Wohlhage, Panteleimon Oikonomou, Markus Schlomm, Eva Mitrova, Michael Beekes, and Inga Zerr.
• Department of Neurology, Clinical Dementia Center and DZNE Georg-August University, Göttingen, Germany. Electronic address: matthias.schmitz@med.uni-goettingen.de.
• Neurobiol. Aging. 2014 May 1; 35 (5): 1177-88.

AbstractThe 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. Copyright © 2014 Elsevier Inc. All rights reserved.

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