title: The diagnostic efficiency of biomarkers in sporadic Creutzfeldt-Jakob disease compared to Alzheimer's disease.
abstract: Laboratory markers have a prominent place among the diagnostic criteria for sporadic Creutzfeldt-Jakob disease (sCJD). Here we investigate the capability of protein 14-3-3, total-tau (t-tau), threonin-181-phosphorylated tau (p-tau), and neuron-specific enolase (NSE) in cerebrospinal fluid (CSF) together with the prion protein gene genotype to discriminate patients with sCJD (n=21) from neurological controls (n=164) and Alzheimer's disease (AD) patients (n=49). Low p-tau/t-tau ratio was the best single marker for sCJD with 90% specificity against neurological controls at 86% sensitivity whilst NSE was the least accurate with 79% sensitivity at 90% specificity. Many of the sCJD patients had extremely elevated t-tau values but normal values of the AD-marker p-tau. Protein 14-3-3 was very sensitive (95%) although the specificity was relatively low (75%). A combination of elevated t-tau concentration with the presence of 14-3-3 protein in CSF gave the best test specificity of 96% at 84% sensitivity. We conclude that the combination of more than one CSF marker for neurodegeneration can improve the diagnostic test accuracy for sCJD against neurological controls including patients with other dementias.
authors.affiliation: Department of Autoimmunology, Statens Serum Institut, Copenhagen, Denmark. jmc@ssi.dk
authors.forename: Justyna Maria Czarna
authors.initials: JM
authors.lastname: Bahl
authors.forename: Niels H H
authors.initials: NH
authors.lastname: Heegaard
authors.forename: Gerhard
authors.initials: G
authors.lastname: Falkenhorst
authors.forename: Henning
authors.initials: H
authors.lastname: Laursen
authors.forename: Hans
authors.initials: H
authors.lastname: Høgenhaven
authors.forename: Kåre
authors.initials: K
authors.lastname: Mølbak
authors.forename: Cathrine
authors.initials: C
authors.lastname: Jespersgaard
authors.forename: Lotte
authors.initials: L
authors.lastname: Hougs
authors.forename: Gunhild
authors.initials: G
authors.lastname: Waldemar
authors.forename: Peter
authors.initials: P
authors.lastname: Johannsen
authors.forename: Michael
authors.initials: M
authors.lastname: Christiansen
mesh_terms: D048948:14-3-3 Proteins / Q000134:cerebrospinal fluid; D000544:Alzheimer Disease / Q000175:diagnosis*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D007562:Creutzfeldt-Jakob Syndrome / Q000175:diagnosis*; D006801:Humans; D010751:Phosphopyruvate Hydratase / Q000134:cerebrospinal fluid; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics; D018709:Statistics, Nonparametric; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D048948:14-3-3 Proteins; D015415:Biomarkers; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D016875:tau Proteins; D010751:Phosphopyruvate Hydratase