Cerebrospinal fluid total tau concentration predicts clinical phenotype in Huntington's disease.
Cerebrospinal fluid total tau concentration predicts clinical phenotype in Huntington's disease.
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DOI：
10.1111/jnc.13719
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发表时间：
2016-10
影响因子：
4.7
通讯作者：
Wild EJ
中科院分区：
文献类型：
--
作者：
Rodrigues FB;Byrne L;McColgan P;Robertson N;Tabrizi SJ;Leavitt BR;Zetterberg H;Wild EJ
亨廷顿病（HD）是一种遗传性神经退行性疾病，已知没有治疗干预可以改变疾病进展，但几项试验正在进行中，需要疾病进展的生物标志物。Tau是一种轴突蛋白，在神经退行性变中经常发生改变，最近的研究指出其在HD神经病理学中的作用。我们的目标是研究脑脊液（CSF）tau蛋白是否是HD疾病进展的生物标志物。知情同意后，从两家HD诊所招募健康对照、症状前和症状性基因扩增携带者。所有参与者都接受了统一HD评定量表'99（UHDRS）的评估。根据标准化腰椎穿刺方案获得CSF。使用酶联免疫吸附试验定量CSF tau。两组之间的比较采用协方差分析。计算疾病进展的Pearson相关系数。显著性水平定义为p < 0.05。76名受试者被纳入这项横断面多中心国际初步研究。与健康对照组相比，基因扩增携带者的年龄校正CSF tau显著升高（p = 0.002）。校正年龄后，UHDRS总功能能力与CSF tau显著相关（r =-0.29，p = 0.004），校正年龄后，UHDRS总运动评分与CSF tau显著相关（r = 0.32，p = 0.002）。几项UHDRS认知任务也与年龄调整后的CST总tau显著相关。这项研究证实，与健康对照相比，HD基因突变携带者的CSF tau浓度增加，并首次报告CSF tau浓度与HD的表型变异性相关。这些结论加强了CSF tau作为HD生物标志物的情况。 在亨廷顿病的新靶向方法时代，需要可靠的生物标志物。我们定量了脑脊液中的Tau蛋白（神经元死亡的标志物），发现它在亨廷顿病患者中增加，并预测患者的运动、认知和功能障碍。因此，它可能是疾病进展的生物标志物，也可能是治疗反应的生物标志物。 阅读第9页上的这篇文章的编辑摘要。
Huntington's disease (HD) is a hereditary neurodegenerative condition with no therapeutic intervention known to alter disease progression, but several trials are ongoing and biomarkers of disease progression are needed. Tau is an axonal protein, often altered in neurodegeneration, and recent studies pointed out its role on HD neuropathology. Our goal was to study whether cerebrospinal fluid (CSF) tau is a biomarker of disease progression in HD. After informed consent, healthy controls, pre‐symptomatic and symptomatic gene expansion carriers were recruited from two HD clinics. All participants underwent assessment with the Unified HD Rating Scale ’99 (UHDRS). CSF was obtained according to a standardized lumbar puncture protocol. CSF tau was quantified using enzyme‐linked immunosorbent assay. Comparisons between two groups were tested using ancova. Pearson's correlation coefficients were calculated for disease progression. Significance level was defined as p < 0.05. Seventy‐six participants were included in this cross‐sectional multicenter international pilot study. Age‐adjusted CSF tau was significantly elevated in gene expansion carriers compared with healthy controls (p = 0.002). UHDRS total functional capacity was significantly correlated with CSF tau (r = −0.29, p = 0.004) after adjustment for age, and UHDRS total motor score was significantly correlated with CSF tau after adjustment for age (r = 0.32, p = 0.002). Several UHDRS cognitive tasks were also significantly correlated with CST total tau after age‐adjustment. This study confirms that CSF tau concentrations in HD gene mutation carriers are increased compared with healthy controls and reports for the first time that CSF tau concentration is associated with phenotypic variability in HD. These conclusions strengthen the case for CSF tau as a biomarker in HD. In the era of novel targeted approaches to Huntington's disease, reliable biomarkers are needed. We quantified Tau protein, a marker of neuronal death, in cerebrospinal fluid and found it was increased in patients with Huntington's disease and predicted motor, cognitive, and functional disability in patients. It is therefore likely to be a biomarker of disease progression, and possibly of therapeutic response. Read the Editorial Highlight for this article on page 9.
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影响因子：
15.9
作者：
Wild, Edward J.;Boggio, Roberto;Weiss, Andreas
通讯作者：
Weiss, Andreas
影响因子：
8.6
作者：
Reilmann, Ralf;Leavitt, Blair R.;Ross, Christopher A.
通讯作者：
Ross, Christopher A.
脑脊液和血液中轻度创伤性脑损伤的生物标志物。
DOI：
10.1038/nrneurol.2013.9
发表时间：
2013-04
期刊：
Nature reviews. Neurology
影响因子：
--
作者：
Zetterberg H;Smith DH;Blennow K
通讯作者：
Blennow K
DOI：
10.1093/brain/awv107
发表时间：
2015-07
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Vuono R;Winder-Rhodes S;de Silva R;Cisbani G;Drouin-Ouellet J;REGISTRY Investigators of the European Huntington’s Disease Network;Spillantini MG;Cicchetti F;Barker RA
通讯作者：
Barker RA
影响因子：
82.9
作者：
Fernandez-Nogales, Marta;Cabrera, Jorge R.;Lucas, Jose J.
通讯作者：
Lucas, Jose J.