Clinical Utility and Correlates of Cerebrospinal Fluid 14-3-3 Protein in the Evaluation of Rapid Progressive Dementia

Background: The 14-3-3 protein in cerebrospinal fluid (CSF) is a suitable marker for the differential diagnosis of patients with rapidly progressive dementia (RPD) suspected of Creutzfeldt-Jakob disease (CJD). However, the CSF 14-3-3 protein has also been detected in various non-prion-related RPD. Our objective was to investigate the general distribution of RPD with positive 14-3-3 result and to evaluate the association between CSF 14-3-3 protein and the clinical features, auxiliary examination and prognosis in patients with RPD. Methods A total of 317 patients with RPD were enrolled in this study and followed-up for at least 2 years. The clinical, auxiliary examination and prognostic data were collected. The CSF 14-3-3 test was performed for all patients, and the distribution of various diseases with a positive 14-3-3 result was analyzed. The patients were divided into the CJD and non-prion RPD groups, and the association of CSF 14-3-3 with clinical features, auxiliary examination and prognosis were tested in both groups. Results The 14-3-3 protein test was positive in a broad spectrum of diseases with RPD, and the most frequent diagnosis was CJD, followed by non-prion disorders like autoimmune encephalitis and neurodegenerative disease. In the CJD group, the positive rate was 50.3%, and CSF 14-3-3 protein was associated with shorter survival ( p  = 0.031), advanced stage ( p  = 0.018), and visual ( p  = 0.045) and cerebellar dysfunction ( p  = 0.025). In the non-prion RPD group, the positive rate was 23.3%, and 14-3-3 protein was more common in the older patients ( p  = 0.028) and those presenting myoclonus ( p  = 0.008). Conclusions The clinical characteristics of patients with positive 14-3-3 test differed significantly from those with the negative result in both the CJD and non-prion RPD groups. In the non-prion RPD group, CSF 14-3-3 protein was more common in patients with myoclonus.