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

From the Laboratory of Neurological Investigation, Cognitive and Behavioral Neurology Unit, Department of Neurology, University of São Paulo School of Medicine, Brazil.

Address correspondence and reprint requests to Dr. N. Huang, Av. Dr. Arnaldo, 455, Faculdade de Medicina da USP, 4o andar, sala 4110, Cerqueira César, São Paulo, SP, CEP: 01246-906, Brazil; e-mail: nancy{at}lim15.fm.usp.br

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.

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