The total tau (t-tau) concentration measured in either cerebrospinal fluid (CSF) or blood is strongly associated with survival time in sporadic Creutzfeldt-Jakob disease (CJD) and may support the potential for several fluid biomarkers as prognostic tools, according to a study published in JAMA Neurology.
For this longitudinal cohort study, patients with probable and pathology-proven sporadic CJD (N=188) were referred to the University of California, San Francisco Memory and Aging Center from March 2004 through January 2018. Patients underwent all or several of the following: cognitive testing, informant measures, standardized neurological examination, and CSF and blood sample collection. The first fluid sample was selected in cases where samples had been collected at multiple time points. Investigators used 5 separate Cox proportional hazard models to calculate survival time (in continuous months) from 5 potential nonfluid biomarkers (ie, sex, age, codon 129 genotype, Barthel Index, and Medical Research Council (MRC) scale). Variables that were significant were used as covariates in subsequent analyses of fluid biomarkers. All fluid biomarkers in separate Cox proportional hazard models were evaluated to assess whether all remained significantly associated with survival in this smaller sample.
Investigators report strong correlations between plasma and CSF neurofilament light (NfL) concentrations (r=0.8; 95% CI, 0.6-0.91; P <.001), as well as between plasma and CSF t-tau concentrations (r=0.74; 95% CI, 0.48-0.88; P <.001). There was also a correlation between CSF t-tau and CSF NfL concentrations (r=0.37; 95% CI, 0.09-0.59; P =.01). The nonfluid biomarkers significantly associated with survival were the Barthel Index, MRC Scale, and codon 129 genotype. Lower baseline levels of function predicted a faster disease course. Greater baseline levels of plasma t-tau and CSF NfL levels were associated with shorter survival times. After controlling for Barthel Index and codon 129 genotype, the association of plasma t-tau level with survival time remained. Plasma t-tau level and Barthel Index (hazard ratio [HR] 0.98; 95% CI, 0.96-0.99; P =.008) had independent value in predicting survival.
This study was limited by its relatively small subsample of patients with all plasma and CSF biomarkers. These results require independent validation in a larger study. Additionally, plasma biomarkers were assayed using a research protocol, as such future studies should use well-validated commercial assays.
Study investigators demonstrated that “plasma t-tau concentration in patients with [sporadic] CJD is a significant predictor of survival.” Plasma t-tau level is more strongly associated with survival than CSF t-tau levels, which is encouraging as blood-based biomarkers are less invasive to obtain compared to CSF. These biomarkers are promising markers of survival time in sporadic CJD, along with functional status and codon 129 polymorphisms, and should be considered when designing future clinical trials.
Several authors disclose affiliations with pharmaceutical companies. Please see the reference for a full list of disclosures.
Staffaroni AM, Kramer AO, Casey M, et al. Association of blood and cerebrospinal fluid Tau level and other biomarkers with survival time in sporadic Creutzfeldt-Jakob disease [published online May 6, 2019]. JAMA Neurol. doi: 10.1001/jamaneurol.2019.1071