14-3-3 protein, total tau and phosphorylated tau in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan
14-3-3 protein, total tau and phosphorylated tau in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan
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DOI：
10.1007/s10571-006-9370-z
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发表时间：
2006-02-01
影响因子：
4
通讯作者：
Matsuo, H
中科院分区：
文献类型：
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作者：
Satoh, K;Shirabe, S;Matsuo, H
1. 散发性克雅氏病（CJD）是一种快速进展且致命的疾病。克雅氏病患者通常会在大约 6 个月内出现运动不能性沉默症。此外，散发性克雅氏病早期的临床症状和体征可能不易通过神经学检查结果与其他神经退行性疾病区分开来。然而，包括14-3-3蛋白、S100、脑脊液(CSF)中神经元特异性烯醇化酶在内的诊断生化参数已被用作诊断标记物，在其他神经退行性疾病的CSF中也可以观察到这些标记物滴度升高。因此，我们检查了其他生化标志物，以将克雅氏病与脑脊液中的其他神经退行性疾病区分开来。2。我们通过 14-3-3 蛋白的蛋白质印迹、总 tau (t-tau) 蛋白和磷酸化 tau (p-tau) 蛋白的定量分析了来自 100 名患有各种神经退行性疾病的患者的脑脊液样本。本研究中所有克雅氏病患者的脑脊液中 14-33 蛋白均呈阳性，且 t-tau 蛋白升高（> 1000 pg/mL）。我们还在非 CJD 组的 2 名患者（阿尔茨海默型痴呆患者；DAT）中检测到 14-3-3 蛋白阳性条带，并在非 CJD 组的 3 名患者中检测到 t- tau 蛋白升高。在两名 DAT 患者和一名急性期脑血管疾病患者中观察到 t-tau 蛋白水平升高。 3．为了区分脑脊液中t-tau蛋白升高的克雅氏病患者和非克雅氏病患者，我们比较了p-tau蛋白和t-tau蛋白的比率。 DAT患者的p-/t-tau比值显着高于CJD患者。4．因此，我们得出的结论是，t-tau 蛋白测定可用作第一次筛选，p-tau 蛋白/t-tau 蛋白的比率可用作第二次筛选，以区分克雅氏病和其他神经退行性疾病。
1. Sporadic Creutzfeldt- Jakob disease ( CJD) is a rapidly progressive and fatal disease. Patients with CJD usually become akinetic mutism within approximately 6 months. In addition, clinical signs and symptoms at early stage of sporadic CJD may not be easy to distinguish from other neurodegenerative diseases by neurological findings. However, diagnostic biochemical parameters including 14- 3- 3 protein, S100, neuron- specific enorase in cerebrospinal fluid ( CSF) have been used as diagnostic markers, elevated titers of these markers can also be observed in CSF in other neurodegenerative diseases. Therefore, we examined other biochemical markers to discriminate CJD from other neurodegenerative diseases in CSF.2. We analyzed CSF samples derived from 100 patients with various neurodegenerative disorders by Western blot of 14- 3- 3 protein, quantification of total tau ( t- tau) protein, and phosphorylated tau ( p- tau) protein. All patients with CJD in this study showed positive 14- 33 protein and elevated t- tau protein (> 1000 pg/ mL) in CSF. We also detected positive 14- 3- 3 protein bands in two patients in non- CJD group ( patients with dementia of Alzheimer's type; DAT) and also detected elevated t- tau protein in three patients in non- CJD group. Elevated t- tau protein levels were observed in two patients with DAT and in one patient with cerevrovascular disease in acute phase.3. To distinguish patients with CJD from non- CJD patients with elevated t- tau protein in CSF, we compared the ratio of p- tau and t- tau proteins. The p-/ t- tau ratio was dramatically and significantly higher in DAT patients rather than in CJD patients.4. Therefore, we concluded that the assay of t- tau protein may be useful as 1st screening and the ratio of p- tau protein/ t- tau protein would be useful as 2nd screening to discriminate CJD from other neurodegenerative diseases.