Department of Neurology, Chang Gung Memorial Hospital, Chang-Gung University College of Medicine, Taipei, Taiwan, People's Republic of China.
PLoS One. 2011 Jan 31;6(1):e15809. doi: 10.1371/journal.pone.0015809.
Huntington's disease (HD) is a progressive neurodegenerative disease caused by an unstable CAG trinucleotide repeat expansion. The need for biomarkers of onset and progression in HD is imperative, since currently reliable outcome measures are lacking. We used two-dimensional electrophoresis and mass spectrometry to analyze the proteome profiles in cerebrospinal fluid (CSF) of 6 pairs of HD patients and controls. Prothrombin, apolipoprotein A-IV (Apo A-IV) and haptoglobin were elevated in CSF of the HD patients in comparison with the controls. We used western blot as a semi-quantified measurement for prothrombin and Apo A-IV, as well as enzyme linked immunosorbent assay (ELISA) for measurement of haptoglobin, in 9 HD patients and 9 controls. The albumin quotient (Qalb), a marker of blood-brain barrier (BBB) function, was not different between the HD patients and the controls. The ratios of CSF prothrombin/albumin (prothrombin/Alb) and Apo A-IV/albumin (Apo A-IV/Alb), and haptoglobin level were significantly elevated in HD. The ratio of CSF prothrombin/Alb significantly correlated with the disease severity assessed by Unified Huntington's Disease Rating Scale (UHDRS). The results implicate that increased CSF prothrombin, Apo A-IV, and haptoglobin may be involved in pathogenesis of HD and may serve as potential biomarkers for HD.
亨廷顿病（HD）是一种由不稳定的 CAG 三核苷酸重复扩展引起的进行性神经退行性疾病。在 HD 中，需要有起始和进展的生物标志物，因为目前缺乏可靠的结果测量方法。我们使用二维电泳和质谱分析法分析了 6 对 HD 患者和对照组的脑脊液（CSF）中的蛋白质组谱。与对照组相比，HD 患者的 CSF 中凝血酶原、载脂蛋白 A-IV（Apo A-IV）和触珠蛋白升高。我们使用 Western blot 作为凝血酶原和 Apo A-IV 的半定量测量方法，以及酶联免疫吸附测定（ELISA）来测量触珠蛋白，在 9 名 HD 患者和 9 名对照组中进行了测量。白蛋白商（Qalb）是血脑屏障（BBB）功能的标志物，在 HD 患者和对照组之间没有差异。CSF 凝血酶原/白蛋白（凝血酶原/Alb）和 Apo A-IV/白蛋白（Apo A-IV/Alb）的比值以及触珠蛋白水平在 HD 中显著升高。CSF 凝血酶原/Alb 比值与使用统一亨廷顿病评定量表（UHDRS）评估的疾病严重程度显著相关。这些结果表明，CSF 中凝血酶原、Apo A-IV 和触珠蛋白的增加可能与 HD 的发病机制有关，并可能作为 HD 的潜在生物标志物。
