NR APAT
AU Zanusso,G.; Farinazzo,A.; Fiorini,M.; Ferrari,S.; Prelli,F.; Tagliavini,F.; Rizzuto,N.; Frangione,B.; Monaco,S.
TI Novel Proteinase K-Resistant Prion Protein Fragments Correlate to Sporadic Creutzfeldt-Jakob-Disease with Different Alleles
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - DG-61
PT Konferenz-Poster
AB
Sporadic Creutzfeldt Jakob disease (sCJD) is the most common human prion disease in humans. The predominant phenotype is represented by a rapidly evolving dementia, myoclonus and by a typical EEG. To date, all the studies on the pathological prion protein (PrPsc) characterization relied on 3F4, a monoclonal antibody which recognize an epitope of 109-112. In this work, we studied 22 subjects with sCJD, with different Met/Val genotypes, and we characterized the PrPsc fragment by using two monoclonal antibodies directed to C-terminal epitopes of the prion protein 6H4 and SP-214. We analyzed by one- and two-dimensional-PAGE (2D-PAGE) the detergent-insoluble PrPsc fraction, the PK resistant core before and after deglycosylation.
After SDS-PAGE analysis we identified novel PK resistant C terminal fragments of 17kDa and 14kDa and 16kDa and 14kDa, comigrating respectively with 21 and 19kDa major fragments. 2D-PAGE analysis showed that in all cases with major fragment of 21kDa, C-terminal fragments separated with specific, reproducible and identical pattern characterized by a trail of spots of 17, 16 and 14kDa, regardless of the genotype. Differently, in cases with a 19kDa PrPsc and Met/Met genotype, C-terminal fragments separated similarly to that observed in 21kDa PrPsc cases, whereas Val/Val and Met/Val subjects showed only spots of 16kDa. Overall, these findings demonstrate that three biochemical groups may be identified in sCJD of different alleles based on specific C-terminal fragment patterns after 2D-PAGE analysis.
AD Gianluigi Zanusso, Alesssia Farinazzo, Michele Fiorini, Sergio Ferrari, Nicola Rizzuto, Salvatore Monaco, Department of Neurological and Visual Sciences, Section of Neurology University of Verona, Verona, Italy; Frances Prelli, Blas Frangione, Department of Pathology, New York University Medical Center, New York, New York, USA; Fabrizio Tagliavini, Istituto Nazionale Neurologico "Carlo Besta", Milano, Italy
SP englisch
PO Deutschland