NR AOEN
AU Bugiani,M.; Rossi,G.; Ironside,J.W.; Will,R.G.; Bugiani,O.; Tagliavini,F.
TI Characteristics and distribution of PrP in the new variant of Creutzfeldt-Jakob disease
QU Journal of Neuropathology and Experimental Neurology 1997; 56(N5): 595 Nr. 98
PT Meeting Abstract
VT A new variant of Creutzfeldt-Jakob disease (CJD) with distinctive clinicopathological features has been identified recently in the UK, and a causal link with bovine spongifonn encephalopathy (BSE) has been suspected. Such a link is supported by the following observations. BSE is transmissible to animals through the oral route; the neuropathologic profile of experimental BSE in macaques is similar to that of variant CJD; the characteristics of the protease-resistant core of the prion protein (PrPres) in variant CJD are distinct from those of other forms of CJD, while are similar to those of naturally or experimentally transmitted BSE. We analysed the electrophoretic mobility and glycosylation pattern of PrPres in samples of cerebral cortex, thalamus and cerebellum of five patients with the new variant of CJD. The results were compared with those obtained in patients with classical CJD, whose brain tissue contained either type 1 or type 2 PrPres (Parchi et al, Ann Neurol 1996), and in one case of BSE. All patients with variant CJD showed the same pattern of PrPres, distinguished by three peptides with electrophoretic mobility of ~ 28, 26 and 19 kDa, respectively. The stoichiometry among these peptides was 1 : 0.68 : 0.32. Deglycosylation resulted in a single band of ~ 19 kDa, indicating that the 28 and 26 PrPres peptides corresponded to different glycoforms, while the 19 kDa peptide was unglycosylated. Quantitative Western blot analysis showed that PrPres accumulated preferentially in the cerebellum and in the thalamus. The biochemical characteristics of PrPres were similar to those of BSE, while were distinct from those of classical CJD. In particular, the protein differed from type 1 PrPres with respect to the electrophoretic mobility and from both type 1 and type 2 PrPrcs with regard to the glycosylation pattern. These findings support the view that the new variant of CJD is caused by a distinct strain of CJD agent, possibly related to the BSE agent.
IN Die scheinbaren Molekularmassen der Proteinase-K-resistenten Prionproteine in den Hirnrinden, den Thalami und den Kleinhirnen von 5 vCJD-Patienten erwiesen sich im Western Blot als gleich mit ~ 28, 26 und 19 kDa und sehr ähnlich wie man es von BSE kennt. Sie unterscheiden sich hinsichtlich der Molekularmassen vom CJD-Typ 1, und hinsichtlich der Mengenverteilung (0,32 : 0,68 : 1) der nicht, einfach bzw. zweifach glykosylierten Formen von den CJD-Typen 1 und 2. Bei der neuen Variante der Creutzfeldt-Jakob-Krankheit akkumulierten die Prionproteine hauptsächlich in Thalamus und Kleinhirn.
ZR 0 Zitate
AD
Bugiani,M.1; Rossi,G.1; Ironside,J.W.2; Will,R.G.2; Bugiani,O.1; Tagliavini,F.1.
1 Istituto Nationale Neurologico Carlo Besta. Milano, Italy,
2 National CJD Surveillance Unit, Western General Hospital, Edinburgh, UK
SP englisch
OR Prion-Krankheiten 2