Cerebrospinal Fluid Biomarker-Based Diagnosis of Sporadic Creutzfeldt-Jakob Disease: A Validation Study for Previously Established Cutoffs

Abstract

Background: Several biomarkers have been proposed to discriminate sporadic Creutzfeldt-Jakob disease (sCJD) from other dementias and control cases. However, their clinical accuracy depends on the PRNP codon 129 genotype, leaving it unclear how well established markers behave in untested conditions. Methods: We analyzed 14-3-3, tau, p-tau levels, and the p-tau/tau ratio in a population sample collected from Polish hospitals including nondementia, dementia, and definite sCJD cases and validated their parameters according to previously established cutoffs. Additionally, the correlation between biomarkers and disease duration as well as the influence of the PRNP129 polymorphism are reported. Results: The tau levels and p-tau/tau ratios differed considerably between sCJD and clinically characterized non-CJD cases (p < 0.001). p-tau was only elevated in sCJD when compared to cases without dementia (p < 0.05). Tau and the p-tau/tau ratio showed a sensitivity of 95 and 100%, respectively, in detecting sCJD cases. A negative correlation between tau levels and disease duration, but not the timing of lumbar puncture was observed. Conclusion: The present findings confirmed the value of the p-tau/tau ratio as a robust sCJD biomarker and suggest a role for tau as prognostic marker.

Cerebrospinal fluid neurofilament light levels in neurodegenerative dementia: Evaluation of diagnostic accuracy in the differential diagnosis of prion diseases

“…Another relevant finding from our study is the potential prognostic value displayed by NFL in sCJD cases, since their levels were negatively correlated with disease duration, as it was previously shown in other dementia-types, especially in AD [2]. Other prion biomarkers such as tau and -synuclein also show a prognostic value for sCJD cases [36,50,51], while data for 14-3-3 [52,53] and RT-QuIC [49,54] are inconsistent.…”

Synaptic, axonal damage and inflammatory cerebrospinal fluid biomarkers in neurodegenerative dementias

“…The 14‐3‐3 proteins are highly expressed in the brain and some of the 14‐3‐3 isoforms are particularly enriched in the presynapses, to regulate transmission and plasticity . The 14‐3‐3 γ protein presents increased levels in the CSF of sporadic CJD and is accepted as part of the current diagnostic criteria . YKL‐40 is a glycoprotein produced by inflammatory cells, mostly astrocytes.…”

CSF nonphosphorylated Tau as a biomarker for the discrimination of AD from CJD

“…Recently, it has been reported that total‐Tau concentrations correlate with disease duration in CJD cases . When allowing for nonlinear associations between t‐Tau and Non‐P‐Tau concentrations and disease duration (time between disease onset and death of the patient), Non‐P‐Tau was able to explain more of the variability in disease duration ( r 2 = 0.19) than total‐Tau ( r 2 = 0.11) in 47 CJD cases were information about disease duration was available.…”