NR ARCS
AU Zerr,I.
TI Cerebrospinal fluid investigations - potential new marker in the clinical diagnosis of prion diseases
QU TSE-Forum, 4. Kongress - Nationale TSE-Forschungsplattform, Düsseldorf 28.10.-29.10.2004, Vortrag V-09
PT Konferenz-Vortrag
AB
The clinical diagnosis in sporadic CJD is supported by the detection of periodic sharp and slow wave complexes in the electroencephalogram (EEG) and hyperintense signals in basal ganglia on magnetic resonance imaging. 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. The sensitivity of these diagnostic techniques varies significantly between phenotypes. Currently, a definite diagnosis of TSE in humans requires autopsy. 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 followed two approaches to establish a more sensitive diagnosis of a prion disease during life time.
1. We attempt to detect the proteinase K resistant form of the prion protein in the CSF by a fluorescent immunoassay using capillary zone electrophoresis as a testing platform. 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.
2. We screened several surrogate markers for their ability to improve the clinical diagnosis, such as cytokines, plasminogen and levels of the normal PrP in CSF. The results are given below:
We could detect abnormal high levels of IL-10 and IL-4 in the CSF of CJD patients. Significant changes were also found for IL-8 and TGF-ß2 in CJD. Of importance, the elevation was significant to other dementia, inflammatory diseases and to controls. TGF-ß 2 was significantly decreased in CSF of CJD compared to all groups. The proinflammatory cytokines IL-1b, IL-12 and TNF-a could not be detected in CSF or in case of IL-6 in only very low concentrations without significant difference.
Following recent findings on possible interaction of plasminogen the abnormal disease-specific prion protein, we analysed plasminogen concentrations and plasminogen activities in patients with CJD and controls. Of interest, patients with CJD had significantly higher plasminogen concentrations than patients with other forms of dementia and plasminogen specific activities were lower in CJD patients.
In another series of experiments, we determined the PrP concentrations in the CSF in CJD, other dementia and normal controls. First data revealed increased PrP levels in CJD in the CSF. Of interest, we could observe an influence of age and codon 129 genotype on PrP concentrations in the CSF.
AD Inga Zerr, Dept. of Neurology, Georg-August University, Göttingen, Germany
SP englisch
PO Deutschland
OR Tagungsband