NR AWCR
AU Cali,I.; Castellani,R.J.; Al-Shekhlee,A.; Zou,W.Q.; Gambetti,P.
TI Classification of sporadic Creutzfeldt-Jakob Disease revisited
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions PR-07
PT Konferenz-Poster
AB Classification of the sporadic form of Creutzfeldt-Jakob disease (sCJD) is based on the molecular size of the unglycosylated isoform of the PK-resistant prion protein (PrPsc) and on the methionine (M)/valine (V) polymorphic genotype at codon 129. In one classification two types of PrPsc are recognized according to the relative molecular mass: ~ 21 kDa (type 1) and ~ 19 kDa (type 2). The PrPsc distinction into two types has supported the view that sCJDMM1, the most representative subtype, is a single entity. However, two other classifications subdivide sCJDMM1 into two different groups based on: 1. three (rather than two) molecular masse types of PrPsc, and 2. distinct phenotypic characteristics, primarily disease duration. To shed light on these divergences, we divided a group of twenty-two subjects with confirmed sCJDMM1 into two sub-populations according to their mean disease duration being 2.02 months (short duration sCJD) and 14.8 months (long duration sCJD). We first focused on the study of the migration in gel of the PrPsc prion protein under those conditions that had led to the detection of the two sCJDMM1 subtypes in the other classifications, under stringent pH conditions and making use of the high resolution gel electrophoresis. We studied the characteristics of PrPsc detected in the two sub-populations using two-dimensional immunoblotting, conformational stability immunoassay, and sucrose gradient fractionation. Moreover, clinical and pathological features were also investigated. The results showed no differences in gel mobility and conformation characteristics of the protease resistant PrPsc between the two populations when sample preparation for homogenization and PK digestion were performed under stringent pH conditions. Phenotypic manifestations were also homogenous except for the presence of more severe lesions in the long duration cases. Therefore, our finding suggests that 1) the variability in gel mobility of PrPsc associated with sCJDMM1 is largely due to the pH variations during tissue homogenization and that 2) the distinction of sCJDMM1 into two subgroups is not justified (Supported by NIH AG-08012 and AG-14359, Charles S. Britton Fund, and CDC UR8/CCU515004).
AD I. Cali, W.Q. Zou, P. Gambetti: Department of Pathology, Case Western Reserve University, Cleveland, USA; A. Al-Shekhlee: Department of Neurology, Case Western Reserve University, Cleveland, USA; R. Castellani: Division of Neuropathology, Department of Pathology, University of Maryland, Baltimore, USA. E-mail: pxg13@case.edu and wenquan.zou@case.edu
SP englisch
PO Italien