NR AXST
AU Mitrova,E.
TI Pathological Prion Protein Deposits and Neurodegenerative Changes in Sporadic and Genetic Creutzfeldt-Jakob Disease Slovak Medical University
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.72
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB The problem, whether neurodegeneration in human prion diseases (PD) are caused by the lack of cellular prion protein (PrPc) or by the toxic effect of pathological prion protein (PrPres) is not solved. Both have support and could probably participate in the development of CNS lesions, but in individual PD their involvement may be different. It is proven that detectable levels of PrPres does not correlate with CNS lesions.The study compares PrPres demonstrated by antiPrP monoclonal antibodies using protease K treated cerebellar slides from sporadic and genetic Creutzfeldt-Jakob disease(CJD) cases. Morphology and intensity of PrPres immunoreactivity (IR) were compared in 25 sporadic and 25 CJD with mutation E200K (CJD-E200K). IR was evaluated as diffuse, patchy or focal. IR findings were correlated with severity of degenerative lesions, M129V polymorphism, age of patients and duration of the clinical stage.Besides of the stripe-like, coarse granular deposits in the cerebellar molecular layer, described previously in CJDE200K patients, other striking difference between sporadic and genetic CJD was found. While sporadic cases showed predominantly diffuse synaptic IR with few granules in the molecular layer and diffuse/patchy granular deposits, with plaques in the granular layer in most of genetic cases IR had only patchy or focal character, synaptic IR was restricted to the deep molecular layer and deposits in the granular layer were less abundant. Besides the different IR pattern comparison revealed evidently more PrPres deposits in cerebella of sporadic comparing to genetic CJDE200K cases. Despite of small amount of PrPres in the genetic CJD-E200K, there was no difference between CJD groups in the severity of spongiform changes in the molecular layer, loss of granular cells, reduced Purkinje cell or high number of axonal torpedoes. No correlation between the IR and the age of patients or duration of the disease was found. Because methionine homozygots predominated in both CJD groups, correlation with polymorphism M129V could not be done. Comparison of PrPres deposits in sporadic and genetic CJD showed in both groups similar neurodegenerative changes but distinct PrPres reactivity, indicating comparable neuronal loss, developing in parallel with different accumulation of pathological PrPres. Lack of correlation between IR and severity of lesions indicate that a neurodegeneration less dependent on PrPres deposits may be involved in pathogenesis of CJD-E200K.
AD E. Mitrová, Slovak Medical University, Slovakia
SP englisch
PO Schottland
EA pdf-Datei und Poster (Postertitel: PrPres deposits and the development of degenerative changes in sporadic and genetic CJD E200K)