Proteomics of human cerebrospinal fluid: Discovery and verification of biomarker candidates in neurodegenerative diseases using quantitative proteomics

Kroksveen, Ann Cathrine; Opsahl, Jill A.; Aye, Tin Tin; Ulvik, Rune J.; Berven, Frode S.

doi:10.1016/j.jprot.2010.11.010

Cited by 127 publications

(117 citation statements)

References 173 publications

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“…24 . The six patients (NN1, NN10, NN20, NN29, NN41 and NN48) did not have any neurological symptoms and thus their CSFs can be regarded as neurologically normal.…”

Section: Relative Quantification Of Human Plasma Protein Markersmentioning

confidence: 99%

“…We first examined the reproducibility, accuracy, dynamic range, assay linearity, labeling efficiency and isotopic effects of this newly developed method, followed by its application to human plasma and cerebrospinal fluid (CSF); both being widely used for biomarker studies and are generally considered among the most challenging samples due to the wide dynamic range of their proteomes. [23][24][25] In addition, we benchmarked the performance of dimethyl-SRM against SID-SRM using CSF. Protein digestion and Stable isotope dimethyl labeling: All protein samples were denatured and digested as described in supplemental information (SI) and the tryptic peptides were desalted using the Oasis® HLB µElution 96 well plate (Oasis, Millipore), vacuum-dried prior to labeling with dimethyl reagents.…”

Section: Introductionmentioning

confidence: 99%

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Use of Stable Isotope Dimethyl Labeling Coupled to Selected Reaction Monitoring to Enhance Throughput by Multiplexing Relative Quantitation of Targeted Proteins

et al. 2012

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In this study we present a proof-of-concept for targeted relative protein quantitation workflow using chemical labeling in the form of dimethylation, coupled with selected reaction monitoring (Dimethyl-SRM). We first demonstrate close to complete isotope incorporation for all peptides tested. The accuracy, reproducibility, and linear dynamic range of quantitation are further assessed based on known ratios of non-human standard proteins spiked into human cerebrospinal fluid (CSF) as a model complex matrix. Quantitation reproducibility below 20% (CV<20%) was obtained for analyte concentrations present at a dynamic range of 4 orders of magnitude lower than that of the background proteins. An error of less than 15% was observed when measuring the abundance of 45 major human plasma proteins. Dimethyl-SRM was further examined by comparing the relative quantitation of eight proteins in human CSF with the relative quantitation obtained using synthetic heavy peptides coupled to stable isotope dilution-SRM (SID-SRM). Comparison between the two methods reveals that the correlation between dimethyl-SRM and SID-SRM is within 0.3-39% variation, demonstrating the accuracy of relative quantitation using dimethyl-SRM. Dimethyl labeling coupled with SRM provides a fast, convenient and cost-effective alternative for relative quantitation of a large number of candidate proteins/peptides.3

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“…24 . The six patients (NN1, NN10, NN20, NN29, NN41 and NN48) did not have any neurological symptoms and thus their CSFs can be regarded as neurologically normal.…”

Section: Relative Quantification Of Human Plasma Protein Markersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Use of Stable Isotope Dimethyl Labeling Coupled to Selected Reaction Monitoring to Enhance Throughput by Multiplexing Relative Quantitation of Targeted Proteins

et al. 2012

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“…The proteomics analysis aims at obtaining a more global and integrated view of biology by studying all the proteins of a cell rather than each one individually. Mass spectrometry is considered an essential tool for proteomic analysis for identification and global semiquantitative measurements of proteins as well as amino acids including protein-protein interaction, protein modifications, protein function, and protein localization studies [33]. Therefore, Verrastro et al [34] studied and detected the amino acids ( Figure 2) by proteomics using Mass Spectrometry.…”

Section: Proteomics and Neurodegenerationmentioning

confidence: 99%

“…Analysis of CSF is an excellent source for identifying biomarkers for neurological diseases as it can be used in studying the biology of neurodegenerative diseases in living patients, and has been used as a major diagnostic tool for a wide range of conditions affecting both the central and the periphery nervous system [38]. By making a comparison between the protein content of CSF in disease and control groups, proteomics and computational software have emerged as a new and promising model for the discovery of new potential biomarkers, this area of research is however still challenging [33]. There are different proteomics techniques that have been used for the categorization of the human CSF proteome including the following:…”

Section: Proteomics and Neurodegenerationmentioning

confidence: 99%

Proteomics Analysis for Therapeutic Options of Neurodegeneration: A Review

Ganash¹

2017

J Proteomics Bioinform

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“…Ultimately, treatment programs could be tailored to the patient's need to improve outcomes. (Kroksveen et al, 2011). More targeted approaches to identify biomarkers based on PD pathophysiology have shown disease-related proteins as strong candidates.…”

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confidence: 99%