Rüetschi Ulla, Zetterberg Henrik, Podust Vladimir N, Gottfries Johan, Li Susann, Hviid Simonsen Anja, McGuire James, Karlsson Mats, Rymo Lars, Davies Huw, Minthon Lennart, Blennow Kaj
Institute of Laboratory Medicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg University, Sweden.
Exp Neurol. 2005 Dec;196(2):273-81. doi: 10.1016/j.expneurol.2005.08.002. Epub 2005 Sep 8.
This investigation describes the discovery of novel possible cerebrospinal fluid (CSF) biomarkers for frontotemporal dementia (FTD) using surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS). Sixteen clinically diagnosed FTD patients and 12 non-demented controls were included in the study. CSF was collected and analyzed for protein expression by SELDI-TOF MS. The samples were analyzed on four different array surfaces using two different energy-absorbing molecules as matrices. In total each sample was subjected to eight different surface/matrix conditions. About 2000 protein peaks (mass/charge ratios) were detected. Forty-two peaks were differentially expressed in FTD (P < 0.01). After exclusion of peaks with low signal-to-noise ratio and/or poor resolution and peaks representing differentially charged proteins, 10 peaks remained, five of which were increased and five decreased in FTD cases compared to controls. Using partial least square discriminant analysis (PLS-DA), the combination of these biomarkers discriminated FTD from non-demented controls with a sensitivity of 94%, a specificity of 83% and an accuracy of 89%. Five of the peaks were purified further and identified by tandem MS as a fragment of neurosecretory protein VGF, transthyretin, S-cysteinylated transthyretin, truncated cystatin C and a fragment of chromogranin B. With use of these potential biomarkers, FTD can be distinguished from control subjects with high accuracy in this pilot study.
本研究描述了使用表面增强激光解吸/电离飞行时间（SELDI-TOF）质谱（MS）发现用于额颞叶痴呆（FTD）的新型脑脊液（CSF）生物标志物的过程。该研究纳入了16例临床诊断为FTD的患者和12名非痴呆对照。收集脑脊液并通过SELDI-TOF MS分析蛋白质表达。使用两种不同的能量吸收分子作为基质，在四种不同的阵列表面上对样品进行分析。每个样品总共接受八种不同的表面/基质条件。检测到约2000个蛋白质峰（质荷比）。FTD中有42个峰差异表达（P <0.01）。在排除信噪比低和/或分辨率差的峰以及代表不同电荷蛋白质的峰后，剩下10个峰，与对照相比，FTD病例中有5个峰升高，5个峰降低。使用偏最小二乘判别分析（PLS-DA），这些生物标志物的组合将FTD与非痴呆对照区分开来，灵敏度为94%，特异性为83%，准确率为89%。其中5个峰进一步纯化并通过串联MS鉴定为神经分泌蛋白VGF的片段、转甲状腺素蛋白、S-半胱氨酸化转甲状腺素蛋白、截短的胱抑素C和嗜铬粒蛋白B的片段。在这项初步研究中，使用这些潜在的生物标志物可以高精度地区分FTD和对照受试者。
