Cerebrospinal fluid markers in the differentiation of molecular subtypes of sporadic Creutzfeldt−Jakob disease

Background and purpose Cerebrospinal fluid (CSF) analysis supports the clinical diagnosis of sporadic Creutzfeldt−Jakob disease (sCJD) when applied within an adequate clinical context. A diagnostic potential has been attributed to CSF proteins such as 14-3-3, but also tau protein, phosphorylated tau (181P) (p-tau) protein, amyloid β1–42, S100B and neuron-specific enolase (NSE). There has been only limited information available about the contribution of CSF analysis in the differentiation of various molecular sCJD subtypes. Methods The CSF levels of the aforementioned proteins from 73 sCJD patients with distinct molecular subtypes were determined. Results Differences in tau values were significant amongst the homozygous patients (MM and VV genotype) compared to the heterozygous group (P = 0.07 and P = 0.02 respectively). Significantly higher CSF tau levels (P = 0.003) and NSE (P = 0.02) but lower p-tau/tau ratio (P = 0.01) were observed in MM1 compared to MM2 patients. The p-tau/tau ratio enabled the differentiation of MV genotype with higher levels in PrPsc type 2 (P = 0.04). Elevation of S100B (P < 0.001) and NSE (P = 0.03) was observed in VV2 compared to VV1 subtype. PRNP codon 129 genotype, PrPsc isotype, disease duration and clinical stage influenced the test sensitivity in all proteins. Conclusions Cerebrospinal fluid protein levels might be useful in the pre-mortem differentiation of molecular sCJD subtypes when the codon 129 genotype is known.