Journal
CELLULAR AND MOLECULAR NEUROBIOLOGY
Volume 26, Issue 1, Pages 45-52Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10571-006-9370-z
Keywords
tau; phosphorylated tau; 14-3-3 protein; diagnosis; cerebrospinal fluid; dementia of Alzheimer type; Creutzfeldt-Jakob disease
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1. Sporadic Creutzfeldt- Jakob disease ( CJD) is a rapidly progressive and fatal disease. Patients with CJD usually become akinetic mutism within approximately 6 months. In addition, clinical signs and symptoms at early stage of sporadic CJD may not be easy to distinguish from other neurodegenerative diseases by neurological findings. However, diagnostic biochemical parameters including 14- 3- 3 protein, S100, neuron- specific enorase in cerebrospinal fluid ( CSF) have been used as diagnostic markers, elevated titers of these markers can also be observed in CSF in other neurodegenerative diseases. Therefore, we examined other biochemical markers to discriminate CJD from other neurodegenerative diseases in CSF. 2. We analyzed CSF samples derived from 100 patients with various neurodegenerative disorders by Western blot of 14- 3- 3 protein, quantification of total tau ( t- tau) protein, and phosphorylated tau ( p- tau) protein. All patients with CJD in this study showed positive 14- 33 protein and elevated t- tau protein (> 1000 pg/ mL) in CSF. We also detected positive 14- 3- 3 protein bands in two patients in non- CJD group ( patients with dementia of Alzheimer's type; DAT) and also detected elevated t- tau protein in three patients in non- CJD group. Elevated t- tau protein levels were observed in two patients with DAT and in one patient with cerevrovascular disease in acute phase. 3. To distinguish patients with CJD from non- CJD patients with elevated t- tau protein in CSF, we compared the ratio of p- tau and t- tau proteins. The p-/ t- tau ratio was dramatically and significantly higher in DAT patients rather than in CJD patients. 4. Therefore, we concluded that the assay of t- tau protein may be useful as 1st screening and the ratio of p- tau protein/ t- tau protein would be useful as 2nd screening to discriminate CJD from other neurodegenerative diseases.
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