NR APAU
AU Zerr,I.
TI Towards the early diagnosis of Creutzfeldt-Jakob disease
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Oral sessions OS-27
PT Konferenz-Vortrag
AB Transmissible spongiform encephalopathies (TSE) in humans and animals are fatal neuro-degenerative diseases with long incubation times. They are characterized pathologically by the triad of spongy degeneration, neuronal loss and astrocyte proliferation. The putative cause of these diseases is a normal host protein, the prion protein, which becomes altered. This abnormal prion protein is found mostly in the brains of infected individuals. Currently, a definite diagnosis of TSE in humans requires autopsy. Some clinical tests such as EEG and MRI support the diagnosis at later stages. In recent years, the analysis of the cerebrospinal fluid (CSF) expands the spectrum of clinical diagnostic techniques. The detection of abnormal high levels of neuronal proteins such as 14-3-3 in the CSF in patients affected by TSE is now established as a sensitive marker of neuronal loss and is helpful in the differential diagnosis of dementia. However, disease specific marker are needed for definite diagnosis of TSE during life time, but this approach requires highly sensitive techniques, since the overall concentration of the abnormal prion protein is presumably low in CSF. In our study, we adapted the methodology of the capillary electrophoresis for detection of the proteinase K resistant form of the prion protein in the CSF. CSF was obtained from patients with definite and probable sporadic CJD and other dementia and the latter group served as a control. A fluorescent immunoassay using capillary zone electrophoresis as a testing platform was used to test the samples. After treatment with proteinase K, which destroys the normal protein but not the altered one, the CSF was extracted and tested for the abnormal prion protein. First experiences with this methodology indicate the presence of proteinase K resistant material in the CSF from about 40% of the individuals diagnosed with sporadic CJD. This assay might become a promising test for an early diagnosis. However, a careful standardization of the technique is necessary. The method should be evaluated further on a larger group with neurodegenerative diseases and dementia.
AD Inga Zerr, University of Göttingen, Germany
SP englisch
PO Deutschland