The diagnostic efficiency of biomarkers in sporadic Creutzfeldt-Jakob disease compared to Alzheimer's disease

• Published in: Neurobiology of aging 2009-11, Vol.30 (11), p.1834-1841
• Main Authors: Bahl, Justyna Maria Czarna, Heegaard, Niels H.H, Falkenhorst, Gerhard, Laursen, Henning, Høgenhaven, Hans, Mølbak, Kåre, Jespersgaard, Cathrine, Hougs, Lotte, Waldemar, Gunhild, Johannsen, Peter, Christiansen, Michael
• Format: Article
• Language: English
• Subjects: 14-3-3 protein; 14-3-3 Proteins - cerebrospinal fluid; Alzheimer Disease - diagnosis; Alzheimer's disease; Biological and medical sciences; Biomarker; Biomarkers - cerebrospinal fluid; Cerebrospinal fluid; Creutzfeldt-Jakob disease; Creutzfeldt-Jakob Syndrome - diagnosis; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Development. Senescence. Regeneration. Transplantation; Fundamental and applied biological sciences. Psychology; Humans; Internal Medicine; Medical sciences; Neurology; Neuron-specific enolase; Phosphopyruvate Hydratase - cerebrospinal fluid; Phosphorylated tau; Prion Proteins; Prions - genetics; Statistics, Nonparametric; Tau; tau Proteins - cerebrospinal fluid; Vertebrates: nervous system and sense organs
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2008.01.013

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.