Biological and methodical challenges of blood-based proteomics in the field of neurological research

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.