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

Elevated total tau protein (t-τ) in the cerebrospinal fluid (CSF) is routinely used as a marker of Creutzfeldt-Jakob disease (CJD). We hypothesized that CSF t-τ and patients' age may anticipate survival time (ST) also in subjects with familial CJD (f-CJD) as has been shown previously in sporadic CJD (s-CJD).

We analyzed data from the Israeli National CJD Registry from 1991 to 2022. The data included cases of both f-CJD and s-CJD in whom demographic data and CSF t-τ levels were measured, and the date of death was available. Using X-tile software, we determined the optimal cut-off points for continuous variables in survival analysis and found the cut-points for t-τ level and patients' age.

We analyzed data on 183 sequential CJD patients. The data included definite (n = 9), probable (n = 165), and possible (n = 9) CJD cases of whom 120 (61 males) were f-CJD (65.6%) and 63 (35 males) patients were s-CJD (34.4%). The cut-off value of CSF t-τ level was found to be 1,226 pg/mL. It separated ST into two groups, 105 days (interquartile ranges [IQR]: 59-305) in the lower group vs. 59 days (IQR: 29.5-147.5) in the higher, p = 0.0005. Cox analyses showed that for every 100 pg/mL increase in CSF t-τ, ST shortened by 3% in days (Exp β = 1.0003; 95% confidence interval: 1.0001-1.0005). Age had no direct prognostic value but correlated with CSF t-τ levels (rho = 0.243, p < 0.001).

Age and CSF t-τ levels above the cut-off value predict ST shortening in patients with both f-CJD and s-CJD.