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

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• 作者：Matthias Schmitz ; Katharina L眉llmann ; Saima Zafar ; Elisabeth Ebert ; Marie Wohlhage ; Panteleimon Oikonomou ; Markus Schlomm ; Eva Mitrova ; Michael Beekes ; Inga Zerr
• 关键词：Biomarker ; Creutzfeldt-Jakob disease ; PrPC charge isoforms ; Truncated PrPC forms
• 刊名：Neurobiology of Aging
• 出版年：May, 2014
• 年：2014
• 卷：35
• 期：5
• 页码：1177-1188
• 全文大小：2874 K

文摘

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.