Cerebrospinal Fluid Levels of a 20-22 kDa NH2 Fragment of Human Tau Provide a Novel Neuronal Injury Biomarker in Alzheimer's Disease and Other Dementias
Cerebrospinal Fluid Levels of a 20-22 kDa NH2 Fragment of Human Tau Provide a Novel Neuronal Injury Biomarker in Alzheimer's Disease and Other Dementias
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DOI：
10.3233/jad-140267
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发表时间：
2014-01-01
影响因子：
4
通讯作者：
Sancesario, Giuseppe
中科院分区：
文献类型：
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作者：
Amadoro, Giuseppina;Corsetti, Veronica;Sancesario, Giuseppe
在包括阿尔茨海默病（AD）在内的几种人类tau蛋白病中，tau蛋白N端结构域的截短与神经病理学早期相关。在受影响的受试者中，监测脑脊液（CSF）中的总（t-tau）和/或磷酸化tau（p-tau）水平可提供对体内发生的细胞变化的可靠、间接评价，鉴定其他CSF生物标志物将更好地协助临床实践，从而更广泛地了解潜在的持续神经变性。在这里，我们显示了20-22 kDa NH 2截短形式的人tau（即，NH（2）htau），我们先前在来自受不同tau蛋白病影响的受试者的突触中发现的全长蛋白（htau 40）的神经毒性片段：（i）不是CSF的正常成分，不像t-tau和p-tau，在没有认知障碍的患者中被异常检测到;（ii）以65%的弱特异性但85%的高灵敏度区分携带与认知退化相关的大范围神经变性疾病的患者（i.例如，AD、额颞叶变性、帕金森病伴痴呆、血管性痴呆、混合性痴呆等）来自受其他神经障碍影响而无记忆障碍的受试者;和（iii）是神经元损伤生物标志物，因为其在CSF中的水平与认知下降的严重程度和进展无关。CSF中NH（2）htau的动态评估可能在普通临床实践中增加一些有用的提示，因为它为人类tau蛋白病和其他与痴呆相关的神经退行性疾病提供了一种新的通用生物标志物。
Truncation at N-terminal domain of tau protein is early associated with neurofibrillary pathology in several human tauopathies, including Alzheimer's disease (AD). In affected subjects, the monitoring of total (t-tau) and/or phosphorylated tau (p-tau) levels in cerebrospinal fluid (CSF) provides a reliable, indirect evaluation of cellular changes occurring in vivo and the identification of additional CSF biomarkers would better assist with the clinical practice, allowing a broader profile of underlying ongoing neurodegeneration. Here we show that a 20-22 kDa NH2-truncated form of human tau (i.e., NH(2)htau), a neurotoxic fragment of the full length protein (htau40) that we previously found in synapses from subjects affected by different tauopathies: (i) is not a normal constituent of CSF, unlike t-tau and p-tau, being exceptionally detected in patients without cognitive impairment; (ii) discriminates, with a weak specificity of 65% but a high sensitivity of 85%, patients carrying a large spectrum of neurodegenerative diseases associated with cognitive deterioration (i. e., AD, frontotemporal lobar degeneration, Parkinson's disease with dementia, vascular dementia, mixed dementia, etc.) from subjects affected by other neurological disorders without mnesic disability; and (iii) is a neuronal injury biomarker as its levels in CSF are not related to the severity and progression of cognitive decline. The dynamic evaluation of NH(2)htau in CSF might add some useful hints in the ordinary clinical practice as it provides a novel, general biomarker for human tauopathies and other neurodegenerative diseases associated with dementia.