NR AOTU
AU Head,M.W.; Peden,A.H.; Ritchie,D.; Smith,N.; Ironside,J.W.
TI Peripheral tissue involvement in variant, but not sporadic Creutzfeldt-Jakob disease
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - PG-03
PT Konferenz-Poster
AB Human prion diseases are rare fatal neurodegenerative conditions that occur as acquired, familial or idiopathic disorders. A key event in their pathogenesis is the accumulation of an altered form of the prion protein, termed PrPsc in the central nervous system. A novel acquired human prion disease, variant Creutzfeldt-Jakob disease (vCJD), is thought to result from oral exposure to the bovine spongiform encephalopathy agent. This disease differs from sporadic Creutzfeldt-Jakob disease (sCJD) in its neurological, neuropathological and biochemical phenotype. We have used immunohistochemistry, Western analysis and PET blotting techniques to analyse the tissue distribution and biochemical properties of protease-resistant prion protein, PrPres, in peripheral tissues in a unique series of vCJD cases. We have compared this with the distribution and biochemical forms found in all of the major subtypes of sCJD. PrPres is detectable in the brain, trigeminal ganglion, eye, spinal cord and dorsal root ganglion in both sporadic and variant CJD. In addition PrPres was detectable in tonsil, spleen, appendix, gastro-intestinal tract and lymph nodes in cases of vCJD. PrPres was found to be undetectable in lung, liver, kidney, muscle and dental tissues in both form of the disease. PrPres accumulated in the lymphoreticular system in vCJD differs from that found in the vCJD brain in terms of glycosylation site occupancy and probably in glycan composition and protein conformation also. These results show that involvement of the lymphoreticular system is a defining feature of variant Creutzfeldt-Jakob disease, but that the biochemical isoform of PrPsc found is influenced by the cell type in which it accumulates.
AD M.W. Head, A.H. Peden, D. Ritchie, N. Smith, J.W. Ironside, National Creutzfeldt-Jakob Disease Surveillance Unit, University of Edinburgh, UK
SP englisch
PO Deutschland