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Ubiquitin as potential cerebrospinal fluid marker of creutzfeldt-jakob disease. |
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AbstractUntil today, a definite diagnosis of Creutzfeldt-Jakob disease (CJD) can only be made neuropathologically. At life time the early and differential diagnosis is often a problem.With SELDI we analyzed cerebrospinal fluid from 32 CJD patients, 32 patients having other dementive diseases and 31 non-demented control subjects for diagnosis dependent protein pattern differences. In a screening set of patients peaks which discriminate best between groups were identified. These peaks were subsequently analysed using an independent validation set of patients. Diagnostic accuracies were compared to established markers like tau protein and 14-3-3-protein. Potential marker proteins were purified and identified by LC-MS/MS.In the validation set only one peak of 8.6 kDa out of ten in the screening set could be confirmed. This protein was identified to be ubiquitin and increased levels in CSF (but not in serum) of CJD patients were confirmed by Westernblot. Ubiquitin allows the correct diagnoses of that CJD cases missed by tau protein or 14-3-3-protein.We conclude that ubiquitin is a promising additional cerebrospinal fluid biomarker for diagnosis of CJD, especially in differential diagnostically difficult cases. The selective increase of ubiquitin in CSF of CJD patients might point to an involvement of ubiquitin in pathophysiological process.
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