Cerebrospinal Fluid Levels of 14-3-3 Gamma: What Does It Tell Us About Sporadic Creutzfeldt-Jakob Disease?

Clinical diagnosis of Creutzfeldt-Jakob disease (CJD) can be supported by the analysis of Tau and 14-3-3 in the cerebrospinal fluid (CSF). In this short report, we report about a retrospective analysis performed on 2,296 routinely collected CSF samples, and 44 samples with a ratio of phosphoTau181/Tau <0.075 were selected. Analysis was performed with a novel 14-3-3 gamma CircuLex Elisa. We show that control levels were around 6,000 AU/mL and samples from Alzheimer patients were not different from those collected from healthy controls. Four cases of verified CJD had 14-3-3 CSF levels of >100,000 AU/mL, while 10 out of 12 suspected CJD samples with 14-3-3 CSF levels between 50,000-100,000 AU/mL were CJD positive. All samples with 14-3-3 levels between 15,000 and 50,000 AU/mL were not CJD cases but disorders with complex neuropathology. In conclusion, our data suggests that in CSF samples with a phospho-Tau-181/Tau ratio <0.075 CSF levels of 14-3-3 should be analyzed. Our data suggests a very high risk for CJD with 14-3-3 levels above 100,000 AU/mL and a probable diagnosis of CJD based on laboratory parameters above 50,000 AU/mL.