Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, S-431 80, Mölndal, Sweden.
Sci Rep. 2018 Mar 9;8(1):4260. doi: 10.1038/s41598-018-21788-x.
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.
亨廷顿病（HD）的生物标志物存在于脑脊液（CSF）中，这可能有助于阐明这种遗传性神经退行性疾病的生物学特性，也有助于开发新的治疗方法。已有研究报道称，HD 存在突触和免疫功能紊乱，在其他神经退行性疾病中，突触蛋白神经颗粒蛋白和小胶质细胞蛋白 TREM2 的浓度增加。因此，我们使用 ELISA 定量测定了 HD 突变携带者和对照组 CSF 样本中的神经颗粒蛋白和 TREM2。与对照组相比，HD 患者的 CSF 神经颗粒蛋白浓度没有显著改变，也与疾病负担评分、总功能能力或运动评分无显著相关性。显性 HD 患者 CSF 中 TREM2 的明显增加被确定是由于 TREM2 随年龄增长而增加。在年龄调整后，无论是在 HD 组中，TREM2 均无明显改变，也与运动、功能或认知评分，或通过 MRI 定量的脑容量无关联。这两种分析都具有很强的功效，样本量计算表明，每组需要数千个样本才能证明疾病相关的改变确实存在。我们得出的结论是，神经颗粒蛋白和 TREM2 均不是用于检测亨廷顿病疾病过程的有用生物液生物标志物。
