title: Cerebrospinal fluid markers in the differentiation of molecular subtypes of sporadic Creutzfeldt-Jakob disease.
abstract: 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.
  
  
  
  The CSF levels of the aforementioned proteins from 73 sCJD patients with distinct molecular subtypes were determined.
  
  
  
  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 PrP(sc) 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, PrP(sc) isotype, disease duration and clinical stage influenced the test sensitivity in all proteins.
  
  
  
  Cerebrospinal fluid protein levels might be useful in the pre-mortem differentiation of molecular sCJD subtypes when the codon 129 genotype is known.
authors.affiliation: Department of Neurology, Clinical Dementia Centre and DZNE, University Medical School, Georg-August University, Göttingen, Germany.|Second Department of Neurology, Comenius University, Bratislava, Slovakia.
authors.forename: K
authors.initials: K
authors.lastname: Gmitterová
authors.affiliation: Department of Neurology, Clinical Dementia Centre and DZNE, University Medical School, Georg-August University, Göttingen, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Heinemann
authors.affiliation: Department of Neurology, Clinical Dementia Centre and DZNE, University Medical School, Georg-August University, Göttingen, Germany.|Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University, Frankfurt, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Krasnianski
authors.affiliation: Department of Neurology, Clinical Dementia Centre and DZNE, University Medical School, Georg-August University, Göttingen, Germany.|Institute for Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Gawinecka
authors.affiliation: Department of Neurology, Clinical Dementia Centre and DZNE, University Medical School, Georg-August University, Göttingen, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Zerr
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002454:Cell Differentiation; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010751:Phosphopyruvate Hydratase / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D055815:Young Adult; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D015415:Biomarkers; D016875:tau Proteins; D010751:Phosphopyruvate Hydratase
keywords: Creutzfeldt−Jakob disease; S100B; cerebrospinal fluid; neuron-specific enolase; tau