NR AXKG
AU Cassard,H.; Uro-Coste,E.; Simon,S.; Bilheude,J.M.; Perret-Liaudet,A.; Ironside,J.W.; Haik,S.; Basset-Leobon,C.; Lacroux,C.; Peoc'h,K.; Streichenberger,N.; Langeveld,J.P.M.; Head,M.W.; Hauw,J.J.; Schelcher,F.; Delisle,M.B.; Andreoletti,O.
TI Beyond the PrPres Type1/ Type2 dichotomy in Creutzfeldt-Jakob Disease
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Natural and Experimental Strains P02.15
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB Creutzfeldt-Jakob disease (CJD) cases are currently classified according to established diagnostic criteria and by the genotype at codon 129 of the PRNP gene and the Western blotting of the proteinase K digested abnormal prion protein that distinguishes a type 1 and a type 2 profile. These biochemically distinct PrPres types have been proposed to represent distinct prion strains. However, since the cooccurence of type 1 and type 2 PrPres in the same patient is common, the rationale of this classification and strain concept as applied to CJD are currently under discussion. Five different brain areas from of 40 sporadic CJD and 11 iatrogenic CJD (both dura matter-, and growth hormone-associated) cases, originating from UK and France, were systematically investigated, using Western blotting typing, and by two others biochemical assays that depend on the behaviour of PrPsc in variable PK digestion conditions. As described previously, co-occurrence of type 1 and type 2 PrPres was found in 30% of the CJD patients examined. However, our novel PK concentration dependent assays identified a single uniform PrP type in cases where both type 1 and type 2 were present. Moreover, in sCJD four distinct biochemical PrPsc signatures were identified by the PK concentration dependent assays and these correlated to the current genotype/clinico-pathological sCJD groups. In iCJD the four similar biochemical signatures were observed, but were not correlated to particular PRNP 129 polymorphism or Western Blot PrPres patterns. Moreover notable differences were observed between PrPsc biochemical properties of French and UK GH-CJD cases, which could reflect, as already suspected, differences in the causative agents. Identification, in sCJD and iCJD, of four different PrPsc phenotypes irrespective of patients PRNP polymorphism at codon 129 and Western blot profile provides new insights into human prion disease aetiology and could reflects an unsuspected diversity of TSE agents in human disease. Further investigations are currently underway using animal transmission to correlate agent strain with our new discriminant biochemical assays.
AD H. Cassard, C. Lacroux, F. Schecher, O. Andreoletti, Ecole Natinale Vétérinaire de Toulouse, France; E. Uro-Coste, C. Basset-Leobon, Service d'Anatomie Pathologique and INSERM U466 R, France; S. Simon, DRM, CEA/Saclay, France; J.M. Bilheude, Bio-Rad, R&D, France; A. Perret-Liaudet, Hôpital Neurologique Service de Neurochimie, France; J. Ironside, School of Molecular & Clinical Medicine (Pathology), National Creutzfeldt-Jakob Disease Surveillance Un, UK; S. Haik, Pitié Salpetriere Universitary Hospital, France; K. Peoc'h, Hôpital Lariboisière, Service de Biochimie et Biologie Moléculaire, France; N. Stressenberger, Hôpital Neurologique -Service de Neurochimie, France; J. Langeveld, CIDC-Lelystad, Netherlands; M. Head, University of Edinburgh, Western General Hospital, UK; J.J. Hauw, Pitié Salpetriere Universitary Hospital, Laboratoire de Neuropathologie, France; M.B. Delisle, Rangueil Universitary Hospital, Service d'Anatomie Pathologique, France
SP englisch
PO Schottland
EA pdf-Datei und Poster (Autorenliste ergänzt um S. Lugan und J. Grassi)