Kasai Takashi, Tokuda Takahiko, Ishii Ryotaro, Ishigami Noriko, Tsuboi Yoshio, Nakagawa Masanori, Mizuno Toshiki, El-Agnaf Omar M A
Department of Neurology, Research Institute for Geriatrics, Kyoto Prefectural University of Medicine, Kyoto, 602-0841, Japan,
J Neurol. 2014 Jun;261(6):1203-9. doi: 10.1007/s00415-014-7334-7. Epub 2014 Apr 16.
Recent studies have shown that cerebrospinal fluid (CSF) levels of α-synuclein (α-syn) are highly elevated in patients with Creutzfeldt-Jakob disease (CJD) compared to controls. However, the diagnostic value of CSF α-syn in CJD has not been established. To confirm whether CSF α-syn is increased in CJD and is a useful marker for this disease, two independent enzyme-linked immunoabsorbent assays (ELISAs) specific for α-syn were used: ELISA 211-FL140, which is specific for full-length α-syn, and ELISA N19-FL140, which is specific for the full-length and associated C-terminal truncated forms of α-syn. CSF samples from 24 patients with CJD and 24 controls were assessed in this study. We found that samples from the CJD patients showed significantly higher levels of CSF α-syn compared to controls in both ELISA (211-FL140 or N19-FL140) tests (P = 0.0467 and P = 0.0010, respectively). However, there was a considerable overlap in the concentration ranges of the two groups of subjects. We also measured the levels of total tau (t-tau) protein in these samples and found that CSF t-tau levels were 5-10-times higher in the CJD group (P < 0.0001) compared with the controls. When the CSF t-tau and α-syn levels were combined, the area under the ROC curve (AUC) was slightly increased in clinically diagnosed CJD cases (AUC of 0.964) relative to an AUC of 0.943 for increased CSF t-tau alone. The combined use of CSF α-syn and t-tau levels may be a useful biomarker for the diagnosis of CJD.
最近的研究表明，与对照组相比，克雅氏病（CJD）患者脑脊液（CSF）中α-突触核蛋白（α-syn）水平显著升高。然而，CSF α-syn在CJD中的诊断价值尚未确立。为了证实CJD患者CSF α-syn是否升高以及它是否是该疾病的有用标志物，我们使用了两种针对α-syn的独立酶联免疫吸附测定（ELISA）：ELISA 211-FL140，它对全长α-syn具有特异性；以及ELISA N19-FL140，它对全长α-syn及其相关的C末端截短形式具有特异性。本研究评估了24例CJD患者和24例对照的CSF样本。我们发现，在两种ELISA（211-FL140或N19-FL140）检测中，CJD患者的样本显示CSF α-syn水平显著高于对照组（P值分别为0.0467和0.0010）。然而，两组受试者的浓度范围有相当大的重叠。我们还测量了这些样本中总tau（t-tau）蛋白的水平，发现CJD组的CSF t-tau水平比对照组高5至10倍（P < 0.0001）。当将CSF t-tau和α-syn水平结合起来时，相对于仅CSF t-tau升高时的曲线下面积（AUC）为0.943，临床诊断的CJD病例的ROC曲线下面积（AUC）略有增加（为0.964）。联合使用CSF α-syn和t-tau水平可能是诊断CJD的有用生物标志物。
