tau protein in cerebrospinal fluid - A biochemical marker for axonal degeneration in Alzheimer disease?
tau protein in cerebrospinal fluid - A biochemical marker for axonal degeneration in Alzheimer disease?
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DOI：
10.1007/bf02815140
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发表时间：
1995-12-01
期刊：
影响因子：
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通讯作者：
Vanmechelen, E
中科院分区：
文献类型：
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作者：
Blennow, K;Wallin, A;Vanmechelen, E
脑脊液生化标记物对提高阿尔茨海默病(AD)的临床诊断准确率具有重要价值。由于微管相关蛋白tau的异常磷酸化形式在AD患者的大脑中一直被发现，而且由于在脑脊液中可以检测到tau，因此基于几种明确的单抗tau的两种检测方法被用于研究脑脊液中的这些蛋白。一种方法检测大多数正常和异常形式的tau(csf-tau)，而另一种方法高度特异地检测磷酸化的tau(csf-phftau)。与对照组(640±230pg/mLp<；0.0001)、血管性痴呆、VAD(1610+/-840pg/mLp<；0.05)、额叶痴呆、FLD(1530+/-1000pg/mLp<；0.05)、帕金森病、PD(720+/-590pg/mLp<；0.0001)和抑郁症(230+/-130pg/mLP<；0.05)组比较，差异有统计学意义。P<；0.0001)。脑脊液-tau蛋白也得到了类似的结果。不少于35/40(88%)的AD患者的脑脊液PHFtau值高于正常对照组的临界值1140 pg/ml。本研究表明AD患者脑脊液中持续存在tau/PHFtau升高。然而，与其他形式的痴呆症仍然存在相当大的重叠，包括VAD和FLD。因此，CSF-tau和CSF-PHFtau可作为一种阳性生化标记物，用于区分AD与正常衰老、PD和抑郁性假性痴呆。需要进一步的研究来阐明这些检测的敏感性和特异性，包括神经病理学检查的后续研究。
Cerebrospinal fluid (CSF) biochemical markers for Alzheimer disease (AD) would be of great value to improve the clinical diagnostic accuracy of the disorder. As abnormally phosphorylated forms of the microtubule-associated protein tau have been consistently found in the brains of AD patients, and since tau can be detected in CSF, two assays based on several well-defined monoclonal tau antibodies were used to study these proteins in CSF. One assay detects most normal and abnormal forms of tau (CSF-tau), while the other is highly specific for phosphorylated tan (CSF-PHFtau). A marked increase in CSF-PHFtau was found in AD (2230 +/- 930 pg/mL), as compared with controls (640 +/- 230 pg/mL; p < 0.0001), vascular dementia, VAD (1610 +/- 840 pg/mL; p < 0.05), frontal Lobe dementia, FLD (1530 +/- 1000 pg/mL; p < 0.05), Parkinson disease, PD (720 +/- 590 pg/mL; p < 0.0001), and patients with major depression (230 +/- 130 pg/mL; p < 0.0001). Parallel results were obtained for CSF-tau. No less than 35/40 (88%) of AD patients had a CSF-PHFtau value higher than the cutoff level of 1140 pg/mL in controls. The present study demonstrates that elevated tau/PHFtau levels are consistently found in CSF of AD patients. However, a considerable overlap is still present with other forms of dementia, both VAD and FLD. CSF-tau and CSF-PHFtau may therefore be useful as a positive biochemical marker, to discriminate AD from normal aging, PD, and depressive pseudodementia. Further studies are needed to clarify the sensitivity and specificity of these assays, including follow-up studies with neuropathological examinations.