Cerebrospinal fluid neurogranin and TREM2 in Huntington's disease.
Cerebrospinal fluid neurogranin and TREM2 in Huntington's disease.
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DOI：
10.1038/s41598-018-21788-x
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发表时间：
2018-03-09
影响因子：
4.6
通讯作者：
Wild EJ
中科院分区：
文献类型：
--
作者：
Byrne LM;Rodrigues FB;Johnson EB;De Vita E;Blennow K;Scahill R;Zetterberg H;Heslegrave A;Wild EJ
脑脊髓液（CSF）中亨廷顿病（HD）的生物标志物可能对阐明这种遗传性神经退行性疾病的生物学以及开发新的治疗方法具有价值。在HD中已经报道了紊乱的突触和免疫功能，并且突触蛋白神经颗粒蛋白和小胶质细胞蛋白TREM2的浓度在其他神经退行性疾病中增加。因此，我们使用ELISA来定量来自HD突变携带者和对照的CSF样品中的神经颗粒蛋白和TREM2。与对照组相比，HD组CSF神经颗粒蛋白浓度无显著变化，与疾病负担评分、总功能能力或运动评分也无显著相关性。确定显性HD中CSF TREM2的明显增加是由于TREM2随年龄增加所致。年龄调整后，两个HD组的TREM2均无显著变化，与运动、功能或认知评分或MRI定量的脑体积也无任何相关性。这两种分析都具有良好的功效，样本量计算表明，每组需要数千个样本来证明疾病相关的改变确实存在。我们的结论是神经颗粒蛋白和TREM2都不是亨廷顿病疾病过程的有用生物流体生物标志物。
Biomarkers of Huntington’s disease (HD) in cerebrospinal fluid (CSF) could be of value in elucidating the biology of this genetic neurodegenerative disease, as well as in the development of novel therapeutics. Deranged synaptic and immune function have been reported in HD, and concentrations of the synaptic protein neurogranin and the microglial protein TREM2 are increased in other neurodegenerative diseases. We therefore used ELISAs to quantify neurogranin and TREM2 in CSF samples from HD mutation carriers and controls. CSF neurogranin concentration was not significantly altered in HD compared to controls, nor was it significantly associated with disease burden score, total functional capacity or motor score. An apparent increase in CSF TREM2 in manifest HD was determined to be due to increasing TREM2 with age. After age adjustment, there was no significant alteration of TREM2 in either HD group, nor any association with motor, functional or cognitive score, or brain volume quantified by MRI. Both analyses were well-powered, and sample size calculations indicated that several thousand samples per group would be needed to prove that disease-associated alterations do in fact exist. We conclude that neither neurogranin nor TREM2 is a useful biofluid biomarker for disease processes in Huntington’s disease.
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影响因子：
4.7
作者：
Rodrigues FB;Byrne L;McColgan P;Robertson N;Tabrizi SJ;Leavitt BR;Zetterberg H;Wild EJ
通讯作者：
Wild EJ
影响因子：
3.4
作者：
Johnson EB;Gregory S;Johnson HJ;Durr A;Leavitt BR;Roos RA;Rees G;Tabrizi SJ;Scahill RI
通讯作者：
Scahill RI
影响因子：
--
作者：
Scahill, RI;Frost, C;Fox, NC
通讯作者：
Fox, NC
影响因子：
3.7
作者：
Rodrigues FB;Byrne LM;McColgan P;Robertson N;Tabrizi SJ;Zetterberg H;Wild EJ
通讯作者：
Wild EJ
影响因子：
5.8
作者：
Ohrfelt, Annika;Axelsson, Markus;Zetterberg, Henrik
通讯作者：
Zetterberg, Henrik