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.