The diagnostic efficiency of biomarkers in sporadic Creutzfeldt-Jakob disease compared to Alzheimer's disease.
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.
Bahl
Justyna Maria Czarna
JM
Department of Autoimmunology, Statens Serum Institut, Copenhagen, Denmark. jmc@ssi.dk
Heegaard
Niels H H
NH
Falkenhorst
Gerhard
G
Laursen
Henning
H
Høgenhaven
Hans
H
Mølbak
Kåre
K
Jespersgaard
Cathrine
C
Hougs
Lotte
L
Waldemar
Gunhild
G
Johannsen
Peter
P
Christiansen
Michael
M
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
D048948:14-3-3 Proteins; D015415:Biomarkers; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D016875:tau Proteins; D010751:Phosphopyruvate Hydratase