14-3-3 protein in the CSF of patients with rapidly progressive dementia.

BACKGROUND: The presence of 14-3-3 protein in the CSF has been described to have high sensitivity and specificity for Creutzfeldt-Jakob disease (CJD). OBJECTIVE: To relate 14-3-3 protein in the CSF with the clinical diagnoses of diseases causing rapidly progressive dementia. METHODS: The authors studied 46 patients with rapidly progressive dementia that was classified into three diagnostic groups: definitive or probable CJD, possible CJD, and other diagnoses. The definitive or probable CJD group comprised 17 patients (3 definitive sporadic, 1 probable iatrogenic, 3 familial, and 10 probable sporadic CJD cases), the possible CJD group was composed of 7 patients, and the group with other diagnoses had 22 patients. Detection of the 14-3-3 protein was done by the immunoblotting method. RESULTS: In the definitive or probable CJD group, the test for 14-3-3 protein in CSF was positive in 14 (82%) cases, whereas 3 patients (1 probable sporadic and 2 familial cases) had negative results. CSF was positive for 14-3-3 protein in three of seven cases with possible CJD (42%). In the group with other diagnoses, three individuals had false-positive results (13%). Their diagnoses were definitive Alzheimer's disease, hypercalcemia, and multiple intracerebral hemorrhages. CONCLUSIONS: The detection of 14-3-3 protein in CSF is a useful in vivo diagnostic test for CJD and, when used in the appropriate clinical context, shows a good correlation to CJD. The presence of the 14-3-3 protein in the CSF reinforces the CJD clinical diagnosis but may not be able to differentiate CJD from other causes of rapidly progressive dementia in everyday clinical practice.

Matrix metalloproteinase profile in patients with Creuztfeldt-Jakob disease.

Preliminary findings suggest that abnormalities in matrix metalloproteinase (MMP) activity may be found in the cerebrospinal fluid (CSF) of patients with Creutzfeldt-Jakob disease (CJD). In this study of 16 subjects with CJD and 16 age-, and sex-matched controls, we determined the presence of MMP-2 and MMP-9 in their active and proenzyme forms, the relative levels of MMP-3 and four inhibitors of MMP activity (TIMP-1, TIMP-2, TIMP-3 and TIMP-4), and the concentration of 4-3-3 protein. The methodology used involved zymography and immunological techniques. The results indicate that, compared with controls, CJD patients have a significantly higher positive frequency of pro-MMP-9 and of the active form of MMP-2, along with significantly higher levels of TIMP-1 and TIMP-2, classical inhibitors of MMP-9 and MMP-2, respectively. We also found a positive correlation between 14-3-3 protein concentration and that of TIMP-1 and TIMP-2 levels (correlation coefficients of 0.793 and 0.798, respectively). These results suggest that abnormalities in MMP and TIMP profiles may be helpful in the biochemical characterisation of CJD.

Iatrogenic Creutzfeldt-Jakob disease following human growth hormone therapy: case report.

We report the case of a 41-year-old man with iatrogenic Creutzfeldt-Jakob disease (CJD) acquired after the use of growth hormone (GH) obtained from a number of pituitary glands sourced from autopsy material. The incubation period of the disease (from the midpoint of treatment to the onset of clinical symptoms) was rather long (28 years). Besides the remarkable cerebellar and mental signs, the patient exhibited sleep disturbance (excessive somnolence) from the onset of the symptoms, with striking alteration of the sleep architecture documented by polysomnography. 14-3-3 protein was detected in the CSF, and MRI revealed increased signal intensity bilaterally in the striatum, being most evident in diffusion-weighted (DW-MRI) sequences. This is the second case of iatrogenic CJD associated with the use of GH reported in Brazil.