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
Department of Autoimmunology, Statens Serum Institut, Copenhagen, Denmark.
Neurobiol Aging. 2009 Nov;30(11):1834-41. doi: 10.1016/j.neurobiolaging.2008.01.013. Epub 2008 Mar 12.
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.
实验室标志物在散发性克雅氏病（sCJD）的诊断标准中占据显著地位。在此，我们研究脑脊液（CSF）中的14-3-3蛋白、总tau蛋白（t-tau）、苏氨酸-181磷酸化tau蛋白（p-tau）和神经元特异性烯醇化酶（NSE）以及朊蛋白基因基因型区分sCJD患者（n = 21）与神经科对照者（n = 164）及阿尔茨海默病（AD）患者（n = 49）的能力。低p-tau/t-tau比值是sCJD的最佳单一标志物，对神经科对照者的特异性为90%，敏感性为86%，而NSE最不准确，敏感性为79%，特异性为90%。许多sCJD患者的t-tau值极高，但AD标志物p-tau的值正常。14-3-3蛋白非常敏感（95%），尽管特异性相对较低（75%）。脑脊液中t-tau浓度升高与14-3-3蛋白同时存在的组合产生了最佳检测特异性，为96%，敏感性为84%。我们得出结论，多种脑脊液神经退行性变标志物的组合可提高sCJD相对于包括其他痴呆患者在内的神经科对照者的诊断测试准确性。
