Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe-University of Frankfurt, Frankfurt am Main, Germany.
Prog Neurobiol. 2013 Feb-Mar;101-102:18-34. doi: 10.1016/j.pneurobio.2012.06.006. Epub 2012 Jun 26.
Biomarker discovery is an application of major importance in today's proteomic research. There is an urgent need for suitable biomarkers to improve diagnostic tools and treatment in various neurological diseases, such as neurodegenerative disorders. Recent years have witnessed an enormous interest in proteomics, which is currently seen as an invaluable tool to shed more light on complex interacting signalling pathways and molecular networks involved in several neuropathological conditions. However, while first results of proteomic research studies have sparked much public attention, the momentum of further proteomic biomarker research in neurological disorders may suffer by its very complex methodology which is sensitive to various sources of artefacts. A major source of variability is proteome perturbation caused by sample handling/preservation (preanalytical phase) and processing/measurement (analytical phase). The aim of the present review is to summarize the current literature focusing on the crucial role played by preanalytical and analytical factors that affect the quality of samples and the reliability of the data produced in blood-based proteomic biomarker research in neurology, which may apply to Alzheimer's disease (AD) as well as other neurological disorders. Procedures for sample preparation and protocols for the analysis of serum and plasma samples will be delineated. Finally, the potential usefulness of bioinformatics--allowing for the assembly, store, and processing of data--as well as its contribution to the execution of proteomic studies will be critically discussed.
生物标志物的发现是当今蛋白质组学研究中的一个重要应用。目前迫切需要合适的生物标志物来改进各种神经疾病（如神经退行性疾病）的诊断工具和治疗方法。近年来，蛋白质组学受到了极大的关注，它目前被认为是一种非常有价值的工具，可以更深入地了解涉及多种神经病理学情况的复杂相互作用的信号通路和分子网络。然而，尽管蛋白质组学研究的初步结果引起了公众的极大关注，但神经紊乱的进一步蛋白质生物标志物研究的势头可能会受到其非常复杂的方法学的影响，这种方法学对各种人为因素很敏感。一个主要的可变性来源是由样品处理/保存（分析前阶段）和处理/测量（分析阶段）引起的蛋白质组扰动。本综述的目的是总结目前的文献，重点介绍分析前和分析因素在影响基于血液的蛋白质生物标志物在神经科学中的研究质量和可靠性方面所起的关键作用，这些因素可能适用于阿尔茨海默病（AD）以及其他神经紊乱。将描述用于样品制备的程序和用于分析血清和血浆样品的方案。最后，将批判性地讨论生物信息学的潜在有用性，允许数据的组装、存储和处理，以及它对蛋白质组学研究执行的贡献。
