NR ATGP
AU Zerr,I.
TI Improvement of the early diagnosis of Creutzfeldt-Jakob disease
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Oral sessions ORAL-46
PT Konferenz-Vortrag
AB
The clinical diagnosis in sporadic CJD is supported by the detection of PSWCs in the EEG and hyperintense signals in basal ganglia on MRI. The detection of abnormal high levels of neuronal proteins such as 14-3-3 in the CSF is now established as a sensitive marker of neuronal loss and is helpful in the differential diagnosis of dementia. Many aspects are not understood, such as factors affecting sensitivity of distinct diagnostic techniques. In a recent EC-based study on diagnostic markers in CJD, a comparative analysis of currently available biochemical parameters was conducted in 3227 samples from CJD patients and controls. We demonstrated that age, disease duration, genetic background and PrPsc type are independent predictors of tests sensitivity for 14-3-3, tau, S100b and enolase. To answer the question, whether the CSF levels of brain-derived proteins correlate with pathology, we analyzed lesion profiles with respect to spongiosis, gliosis and neuronal loss in various brain areas. We identified three different pattern of alteration of brain derived proteins: enolase levels were increased already with minor lesion severity and correlated with lesion severity of subcortical areas (thalamus, nucleus caudatus and putamen). Tau and 14-3-3 levels increased with minor pathological changes too, but a negative correlation could be observed with severity of cortical lesions. PrPc levels and Aß1-42 levels were normal at stages with minor lesions and correlated negatively with cortical pathology. The neuronal loss in temporal and occipital areas correlated best with declining Aß1-42 levels. Our results indicate that the alteration of levels of brain-derived proteins in the CSF does not simply reflect a neuronal damage but might also involve brain-area specific factors.
In summary, the sensitivity of diagnostic techniques varies between molecular CJD subtypes (as reflected by genotype, PrPsc type and neuropathological lesion profiles). To further improve the clinical diagnosis of CJD, biochemical approaches for either detection of abnormal PrPsc or identification of other disease-related markers have to be followed. Data on recent advances in the latter techniques will be presented. In addition, recent evidence supports the introduction of MRI in the diagnostic criteria since subtype specific lesion pattern using high sensitive techniques might allow a premortem clinical classification of particular disease subtype in CJD.
AD I.Zerr, Neurologische Klinik, CJD-Forschungsgruppe, Georg-August-Universität Göttingen, Germany
SP englisch
PO Deutschland