14-3-3 Protein, Neuron-Specific Enolase, and S-100 Protein in Cerebrospinal Fluid of Patients with Creutzfeldt-Jakob Disease

Abstract

We explored simultaneously 14-3-3 protein, neuron-specific enolase (NSE), and one astroglial protein, S-100, recently proposed as Creutzfeld-Jakob disease (CJD) markers, in the cerebrospinal fluid (CSF) of 129 patients with suspected CJD. Cutoff values for NSE and S-100 were established at 25 and 2.5 ng/ml, respectively. The highest sensitivity was observed for S-100 (94.2%) followed by 14-3-3 (89.8%) and NSE (79.7%), while the highest specificity in CJD diagnosis was obtained with 14-3-3 protein (100%) as compared with NSE (91.5%) and S-100 (85.4%). No influence of sex, genotype at codon 129 of the prion protein gene, time between sampling, and death or disease duration has been found. Based on 90 cases initially referred as ‘probable’ or ‘possible’ CJD, with 14-3-3, NSE, or S-100 we could correctly discriminate between ‘CJD’ or ‘non-CJD’ categories in 94.4, 86.5, and 90% of the cases, respectively. When limited to ‘possible CJD’ cases, diagnosis based on one of the three CSF proteins was accurate in 98, 90.7 and 87.3%, respectively. In view of the fact that the CSF 14-3-3 protein test alone has the highest specificity and good sensitivity, it appears that there is no additional advantage at the moment to include NSE and/or S-100 protein in the exploration of clinically suspected CJD cases.

Practice parameter: Diagnosis of dementia (an evidence-based review)

“…104 The additional use of neuron-specific enolase does not appear to substantially improve diagnostic accuracy. 105 Other biomarkers. No other biomarkers that had been extensively studied and had promising detection abilities for AD or other dementias were uncovered in the literature search.…”

Subtype Specific CSF Biomarkers in Sporadic Creutzfeldt-Jakob Disease

“…Neuron-specific enolase (NSE) is reported to be elevated and was one of the first protein with potential for differential diagnosis of Creutzfeldt-Jakob disease from other dementing illnesses [24,[47][48][49][50]. In our sCJD patient cohort homozygous group (MM and VV) showed elevated levels of NSE as compared to the heterozygous [45].…”

The use of non-prion biomarkers for the diagnosis of Transmissible Spongiform Encephalopathies in the live animal

“…Several studies have reported increased abundances of S100B in CSF from patients afflicted with sporadic and variant CJD [7,40,74] and preclinical Alzheimer's disease (AD) [73]. In cattle CSF, S100B levels were significantly elevated in confirmed field cases of BSE when compared to clinically normal controls and to BSE-suspect animals later confirmed as BSE negative by histopathology [39].…”