Phospho-tau/total tau ratio in cerebrospinal fluid discriminates Creutzfeldt-Jakob disease from other dementias
Phospho-tau/total tau ratio in cerebrospinal fluid discriminates Creutzfeldt-Jakob disease from other dementias
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DOI：
10.1038/sj.mp.4001220
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发表时间：
2003-01-01
影响因子：
11
通讯作者：
Kurz, A
中科院分区：
文献类型：
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作者：
Riemenschneider, M;Wagenpfeil, S;Kurz, A
散发性克雅氏病（CJD）的早期临床症状可能与其他神经退行性疾病如阿尔茨海默病（AD）和额颞叶变性（FTD）重叠。在进入CJD药物治疗的时代后，需要可靠的诊断标志物，如脑脊液（CSF）中14-3-3蛋白的免疫检测。然而，尸检证实的散发性CJD病例的假阴性结果，以及其他几种疾病（包括AD和FTD）的假阳性结果显示CSF tau蛋白水平较高，限制了该标志物的潜力。由于神经元裂解，含有磷酸化和非磷酸化同种型的总tau的胞质级分部分释放到CSF中。由于tau蛋白的过度磷酸化可能特异性地发生在与神经退行性病变相关的神经退行性疾病中，因此我们假设CSF中的磷酸化tau蛋白（P-tau）/总tau蛋白比率可能是区分CJD与其他神经退行性疾病的有用标志物。P-tau/总tau比值将CJD患者与所有其他神经退行性疾病（包括AD和FTD患者）区分开来，无任何重叠。虽然结果必须在更大的样本中得到证实，但初步数据表明，同时测量CSF中的总tau和P-tau可能有助于识别CJD患者。
Early clinical symptoms of sporadic Creutzfeldt-Jakob disease (CJD) may overlap with other neurodegenerative diseases like Alzheimer's disease (AD) and frontotemporal degeneration (FTD). On entering an era in which pharmaceutical treatment of CJD occurs, reliable diagnostic markers like immunodetection of 14-3-3 proteins in the cerebrospinal fluid (CSF) are required. However, false negative results in autopsy-proven, sporadic CJD cases, as well as false positive results in several other disorders including AD and FTD showing high CSF tau protein levels, limit the potential of this marker. Due to neuronal lysis the cytosolic fraction of total tau containing phosphorylated and non-phosphorylated isoforms is partially liberated into the CSF. Since hyperphosphorylation of tau may specifically occur in neurodegenerative diseases associated with neurofibrillary changes, we hypothesized that the phospho-tau (P-tau)/total tau ratio in CSF may be a useful marker to discriminate CJD from other neurodegenerative disorders. The P-tau/total tau ratio discriminated patients with CJD from all other neurodegenerative disorders including patients with AD and FTD without any overlap. Although the results have to be confirmed in a larger sample, the preliminary data suggest that simultaneous measurement of total tau and P-tau in CSF may be useful to identify patients with CJD.