Direct Analytical Sample Quality Assessment (DASQ) for Biomarker Investigation : qualifying CSF samples

The term “neurodegenerative disease” includes a range of different conditions that affect neurons resulting in progressive death of nerve cells. The complexity of human brain and neurological disorders represents a roadblock in identifying biomarkers for an early diagnosis and a targeted treatment. In recent years, proteomics approaches based on mass spectrometry are become an essential tool to investigate the proteome of cerebrospinal fluid (CSF). There are many factors to increase the chances that a proteomic study on CSF biomarkers becomes successful. More than 84% of laboratory errors depend on pre-analytical variables associated with non-optimal sample collection and storage. The development of a standardized protocol based on some procedures for CSF quality control is a mandatory step, especially when samples are collected in different centres. Therefore we propose a direct assessment of sample quality (DASQ) by applying a fast MALDI-TOF-MS methodology to evaluate several molecular features of CSF degradation and oxidation, associated to a sub-optimal storage. We propose DASQ as an initial step to be included in large-scale projects such the BIOMARK-APD, part of the initiative of the Joint Program-Neurodegenerative Disease Research (JPND), to provide new approaches for the comprehension of neurodegenerative diseases. This topic might also be useful to biobanks that support international studies for biomarkers discovery, as HUPO. The emerging technology of MS-based proteomics could become a powerful link between the study of neurodegenerative disease, central focus of JPND, and the core research of HPP centered in proteomics, with a special interest on human biological fluids and related networks.