Department of Neurology, University of Ulm, Ulm, Germany.
J Alzheimers Dis. 2010;22(1):119-28. doi: 10.3233/JAD-2010-100030.
The clinical diagnosis of Creutzfeldt-Jakob disease (CJD) can be supported by several biochemical markers in cerebrospinal fluid (CSF) such as 14-3-3 proteins and tau protein. Unfortunately, none of the currently known markers are suited for screening or seems to be directly related to the pathophysiological process. A marker fulfilling these criteria might facilitate the early detection and might also serve in monitoring drug efficacy. Recently, the extracellular signal-regulated kinase ERK1/2 was detected in CSF of patients with neuropsychiatric disorders. Furthermore, ERK1/2 was reported to be activated in brains of animals infected with pathological prion protein. Therefore, we investigated CSF of 19 patients with CJD, 23 patients with other dementias including patients with Alzheimer's disease, and 12 patients with other neurological disorders. The measurement of ERK1/2 in the CSF samples was performed with an electrochemiluminescence assay and Western immunoblot. ERK1/2 and doubly phosphorylated ERK1/2 (pERK1/2) were detected in all patient groups. Significantly elevated mean levels of total ERK1/2 and pERK1/2 were found in the CJD patients. This increase was also observed in a CJD case that was negative for 14-3-3 protein or in CJD cases that had low levels of tau protein. Western immunoblot analysis suggested that ERK2 was the predominant form of ERKs present in our CSF samples. This pilot study suggests that ERK1/2 is a potential CSF biomarker for CJD, directly associated with the pathophysiological processes. Analysis of larger sample cohorts including other diseases with rapid neurodegeneration are required to confirm our findings.
克雅氏病（CJD）的临床诊断可以通过几种脑脊液（CSF）中的生化标志物得到支持，如 14-3-3 蛋白和 tau 蛋白。不幸的是，目前已知的标志物都不适合用于筛查，也似乎与病理生理过程没有直接关系。符合这些标准的标志物可能有助于早期发现，也可能用于监测药物疗效。最近，细胞外信号调节激酶 ERK1/2 在神经精神疾病患者的 CSF 中被检测到。此外，据报道 ERK1/2 在感染病理性朊病毒蛋白的动物大脑中被激活。因此，我们研究了 19 例 CJD 患者、23 例其他痴呆症患者（包括阿尔茨海默病患者）和 12 例其他神经疾病患者的 CSF。CSF 样本中的 ERK1/2 测量采用电化学发光测定法和 Western 免疫印迹法进行。在所有患者组中均检测到 ERK1/2 和双磷酸化 ERK1/2（pERK1/2）。CJD 患者的总 ERK1/2 和 pERK1/2 水平明显升高。在 14-3-3 蛋白阴性或 tau 蛋白水平较低的 CJD 病例中也观察到这种增加。Western 免疫印迹分析表明 ERK2 是我们 CSF 样本中存在的 ERKs 的主要形式。这项初步研究表明，ERK1/2 是 CJD 的潜在 CSF 生物标志物，与病理生理过程直接相关。需要对包括快速神经退行性疾病在内的其他疾病的更大样本队列进行分析，以确认我们的发现。
