Prognostic Value of CSF Total Tau Protein in Patients with Familial and Sporadic Creutzfeldt-Jakob Disease

Background: Elevated total tau protein (t-τ) in cerebrospinal fluid (CSF) is routinely used as a diagnostic marker of Creutzfeldt-Jakob's disease (CJD). We hypothesized that combined t-τ level in CSF and patient's age may predict survival. Methods: We analyzed data from the Israeli National CJD Registry (1991-2022). Included were cases of familial and sporadic CJD for whom essential demographic details were available, precise t-τ in CSF levels had been measured and recorded and the date of death was available. Survival time was calculated as the difference between the date of death and the date of CSF sampling. We calculated the cut-off points for t-τ level and patient's age by X-tile software, a bioinformatics tool for determining the optimal cut-off points for continuous variables in survival analysis. The patients were dichotomized accordingly, and survival time in each group formed by the various cutoff points were compared. Univariate and multivariate Cox regression analyses then evaluated the relationships between the t-τ in CSF level, patient's age and their influence on survival time. Results: Data on 183 consecutive CJD patients (age range 37-88 years; 96 males [52.5%]) were available for analysis. The median survival time was 83 days (range: 3-971, IQR: 45-233.5). The median t-τ in CSF level was 1151 ng/mg (range: 111-3787, IQR: 693-1519). The t-τ level in CSF cutoff point was 1226 ng/ml, and it divided the survival time into one group of 106 days (IQR: 59-305.8 days) and another group of 59 days (IQR: 30-143), Cox analyses showed that survival time was shortened by 3% for every 100 ng/ml increase in t-τ in CSF (Exp β =1.0003; 95% CI: 1.0001-1.0005; Mann-Whitney, p = 0.0004.). Conclusion: An elevated t-τ in CSF level predicted shortening of survival time and may represent a modest prognostic survival marker in patients with CJD.