Creutzfeldt-Jakob disease (CJD) is characterized by an extended asymptomatic preclinical phase followed by rapid neurodegeneration. There are no effective treatments. CJD diagnosis is initially suspected based upon the clinical presentation of the disease and the exclusion of other etiologies. Neurologic symptoms are assessed in combination with results from cerebrospinal fluid (CSF) biomarker abundances, electroencephalography (EEG), magnetic resonance imaging (MRI), and in some countries, real-time quaking-induced conversion (RT-QuIC). Inconsistencies in sensitivities and specificities of prion disease biomarker abundance in CSF have been described, which can affect diagnostic certainty, but the utility of biomarkers for prognosis has not been fully explored. The clinical presentation of CJD is variable, and factors such as prion protein polymorphic variants, prion strain, and other genetic or environmental contributions may affect the disease progression, confounding the appearance or abundance of biomarkers in the CSF. These same factors may also affect the appearance or abundance of biomarkers, further confounding diagnosis. In this study, we controlled for many of these variables through the analysis of serial samples of CSF from prion-infected and control rats. Prion disease in laboratory rodents follows a defined disease course as the infection route and time, prion strain, genotype, and environmental conditions are all controlled. We measured the relative abundance of 14-3-3 and neuron-specific enolase (NSE) in CSF during the course of prion infection in rats. Even when disease-related, environmental and genetic variables were controlled, CSF 14-3-3 and NSE abundances were variable. Our study emphasizes the considerable diagnostic and prognostic limitations of these prion biomarkers.

克雅氏病（CJD）的特征是无症状的临床前期延长，然后迅速发生神经变性。没有有效的治疗方法。最初基于该疾病的临床表现和其他病因的排除怀疑为CJD诊断。将神经症状与脑脊液（CSF）生物标志物丰度，脑电图（EEG），磁共振成像（MRI）以及某些国家/地区实时地震诱发的转化（RT-QuIC）的结果结合起来进行评估。已经描述了脑脊液中病毒疾病生物标志物丰度的敏感性和特异性不一致，这可能会影响诊断的确定性，但尚未充分探索生物标志物在预后中的作用。CJD的临床表现是可变的，factors病毒蛋白多态性变异，病毒株以及其他遗传或环境因素等因素可能会影响疾病的进展，从而混淆生物标志物在脑脊液中的出现或数量。这些相同的因素也可能会影响生物标志物的出现或数量，进一步混淆诊断。在这项研究中，我们通过分析病毒感染和对照大鼠的脑脊液连续样本来控制许多这些变量。实验室啮齿动物中的病毒疾病遵循明确的病程，因为感染途径和时间，病毒株，基因型和环境条件均受到控制。我们测量了病毒感染大鼠过程中脑脊液中14-3-3和神经元特异性烯醇化酶（NSE）的相对丰度。即使控制了疾病相关的环境和遗传变量，CSF 14-3-3和NSE的丰度是可变的。我们的研究强调了这些病毒生物标志物的相当大的诊断和预后局限。