Prion protein glycotype analysis in familial and sporadic Creutzfeldt-Jakob disease patients

Creutzfeldt-Jakob disease (CJD) and other transmissible spongiform encephal opathies (TSEs) are characterised by the accumulation of a pathological con former of PrP, named PrPsc, Molecular weight and glycosylation of the prote ase-resistant core of PrPsc (PrP27-30) are heterogeneous in different forms of TSEs, We analysed PrP27-30 glycotypes in a large number of TSE-affected patients: 50 sporadic CJD (sCJD), 1 iatrogenic CJD, 1 Gerstmann-Straussler -Scheinker syndrome (GSS) with the Pro102Leu mutation of PrP, 3 familial CJ D (fCJD) with the Glu200Lys mutation and, for the first time, 7 fCJD with t he Val210lle mutation. All patients were screened for the polymorphic codon 129 of the PrP gene. PrP27-30 deglycosylation and PrPsc immunohistochemist ry were performed in selected cases, We found that two PrP27-30 glycotypes (type 1A and type 2A) are produced in sCJD, Type 1A is more frequently asso ciated with methionine than valine in position 129, Type 1A is also formed in Val210lle fCJD. In Glu200Lys fCJD and GSS patients, we found that PrP27- 30 has the same mobility of type 1 but different glycosylation ratios (type 1B), Our findings indicate that the polymorphic residue 129 of PrP has a l eading role in determining the proteinase degradation site of PrPsc while m utant residues 102 or 200 influence only the glycosylation pattern. (C) 199 9 Elsevier Science Inc.