Direct Analytical Sample Quality Assessment (Dasq) For Biomarker Investigation: Qualifying Csf Samples

893 words - 4 pages

It has been just known that pathophysiological processes underlying neurodegenerative diseases are better reflected in the CSF and in its protein content than in other body fluids.
Changes in peptidome and proteome of CSF can be revealed by novel technologies performed on mass spectrometry that could be useful for searching new disease related biomarkers. Among these, MALDI-TOF-MS (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry) is a promising powerful high-throughput approach to investigate new potential biomarkers in biological fluids. MALDI TOF mass spectrometry in linear mode is a fast analysis to investigate the protein profile of CSF and offers some different advantages: guarantees a good resolution (1 Da), a low backgroundlevel, permits to explore the low mass range (5000- 20,000 Da) in order to investigate the low protein and peptide molecular weight region (fig.1) .The amount of samples required for the analysis is minimal and the overall procedure can be automated analysis of high number of samples in a limited amount of time (3 min per/sample). Moreover the protocol of sample preparation is very simple [8].and the costs of analysis are limited in respect to other techniques A direct MALDI-TOF-MS approach for proteomics investigations may lead to the development of novel laboratory tests for clinical molecular markers. In order to develop, validate and implement testing protocols of each CSF marker, it’s necessary to put in place a number of support actions that include the validation of platforms related to the biological markers investigation. Furthermore, according to the aims of BIOMARKAPD to standardize the assessment of established and new fluid biomarkers for AD and PD we have proposed a direct assessment of sample quality (DASQ) by a collaborative project applying a fast MALDI-TOF-MS platform to evaluate simultaneously those molecular features of sample degradation and oxidation associated with non optimal sample collection and storage [30,31].and to provide a direct and analytical evaluation of the collection and storage phases of CSF samplesMALDI TOF MS/MS permits to control the quality of samples that is a mandatory step for clinical proteomics studies. An analysis by MALDI TOF can evaluate all the features that the literature reported so far has just highlighted[30,31].Therefore such an analysis permits simultaneously to check for the presence of blood contamination (e.g. haemoglobin chains) and presence of molecular truncated isoforms (e.g. Cystatin C) and oxidized proteins (e.g Transthyretin) .
Fig. 2 shows how, during collection of CSF, contamination by whole blood, whom protein concentration of whole blood is much higher than in CSF, may independently alter the proteomic profile leading to error of...

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