scholarly journals Proteomic Analysis of Cerebrospinal Fluid Changes Related to Postmortem Interval

2006 ◽  
Vol 52 (10) ◽  
pp. 1906-1913 ◽  
Author(s):  
Erin J Finehout ◽  
Zsofia Franck ◽  
Norman Relkin ◽  
Kelvin H Lee
Keyword(s):  
Oxidative Stress ◽  
Mass Spectrometry ◽  
Cerebrospinal Fluid ◽  
Tandem Mass Spectrometry ◽  
Gel Electrophoresis ◽  
Protein Production ◽  
Postmortem Interval ◽  
Cytoskeletal Proteins ◽  
Tandem Mass ◽  
Concentration Change

Abstract Background: The study of proteins with altered production in postmortem cerebrospinal fluid (CSF) compared with antemortem CSF may improve the understanding of biochemical changes that occur immediately after death. Methods: Two CSF samples (1 antemortem and 1 postmortem) were collected from 7 patients and analyzed by 2-dimensional gel electrophoresis. An analysis was also performed to identify proteins that showed a correlation between concentration change and postmortem interval. Tandem mass spectrometry was used to identify the proteins. Results: Fifty-four protein spots were identified that showed a consistent and significant change in concentration in the postmortem CSF of all 7 patients (>3.5-fold, P <0.01). The proteins in these spots derive from a variety of functional groups, including cytoskeletal proteins, enzymes involved in glycolysis, and proteins that prevent oxidative stress. Fourteen protein spots were found to have an increase in production that correlated with postmortem interval. Conclusions: Changes in protein production of postmortem vs antemortem CSF were studied. The proteins observed to change production in the postmortem CSF include several proteins previously observed as potential stroke biomarkers.

Detection and quantitation of irisin in human cerebrospinal fluid by tandem mass spectrometry

Peptides ◽  
2018 ◽  
Vol 103 ◽  
pp. 60-64 ◽  
Author(s):  
Qingwei Ruan ◽  
Limin Zhang ◽  
Jian Ruan ◽  
Xixue Zhang ◽  
Jie Chen ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cerebrospinal Fluid ◽  
Tandem Mass Spectrometry ◽  
Tandem Mass ◽  
Human Cerebrospinal Fluid

scholarly journals Determination of S-Adenosylmethionine and S-Adenosylhomocysteine in Plasma and Cerebrospinal Fluid by Stable-Isotope Dilution Tandem Mass Spectrometry

2000 ◽  
Vol 46 (10) ◽  
pp. 1650-1656 ◽  
Author(s):  
Eduard A Struys ◽  
Erwin E W Jansen ◽  
Kees de Meer ◽  
Cornelis Jakobs
Keyword(s):  
Mass Spectrometry ◽  
Cerebrospinal Fluid ◽  
Stable Isotope ◽  
Tandem Mass Spectrometry ◽  
Solid Phase ◽  
Extraction Procedure ◽  
Internal Standard ◽  
Tandem Mass ◽  
Analytical Technique

Abstract Background: Available methods for the determination of nanomolar concentrations of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in plasma and cerebrospinal fluid (CSF) are time-consuming. We wished to develop a method for their rapid and simultaneous measurement. Methods: We used tandem mass spectrometry (MS/MS) for the simultaneous determination of SAM and SAH, with stable-isotope-labeled internal standards. The 13C5-SAH internal standard was enzymatically prepared using SAH-hydrolase and [13C5]adenosine. The method comprises a weak anion-exchange solid-phase extraction procedure serving as clean-up step for the deproteinized plasma and CSF samples. After clean-up, samples were injected on a C18 HPLC column, which was connected directly to the tandem mass spectrometer, operating in MS/MS mode. Results: In plasma samples, the intraassay CVs for SAM and SAH were 4.2% and 4.0%, respectively, and the interassay CVs were 7.6% and 5.9%, respectively. In CSF, the intraassay CVs for SAM and SAH were 6.8% and 6.9%, respectively, and the interassay CVs were 4.2% and 5.5%, respectively. Mean recovery of SAM and SAH for both matrices at two concentrations was 93%. Detection limits for SAM and SAH in samples were 7.5 and 2.5 nmol/L, respectively. Concentrations of SAM and SAH in plasma from healthy subjects were within the previously reported ranges. In 10 CSF samples, the mean concentrations (range) were 248 (137–385) nmol/L for SAM and 11.3 (8.9–14.1) nmol/L for SAH. Conclusions: SAM and SAH can be analyzed by MS/MS, taking optimal advantage of the speed and high sensitivity and specificity of this relatively new analytical technique.

scholarly journals Quantification of Tau in Cerebrospinal Fluid by Immunoaffinity Enrichment and Tandem Mass Spectrometry

2014 ◽  
Vol 60 (4) ◽  
pp. 683-689 ◽  
Author(s):  
Thomas McAvoy ◽  
Michael E Lassman ◽  
Daniel S Spellman ◽  
Zhenlian Ke ◽  
Bonnie J Howell ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cerebrospinal Fluid ◽  
Tandem Mass Spectrometry ◽  
Magnetic Beads ◽  
Internal Standard ◽  
Tandem Mass ◽  
Limit Of Quantification ◽  
Total Tau ◽  
Liquid Chromatography Tandem Mass ◽  
Full Scan

Abstract BACKGROUND Cerebrospinal fluid (CSF) tau is a common biomarker for Alzheimer disease (AD). Measurements of tau have historically been performed using immunoassays. Given the molecular diversity of tau in CSF, the selectivity of these immunoassays has often been questioned. Therefore, we aimed to develop an analytically sensitive and selective immunoaffinity liquid chromatography–tandem mass spectrometry (LC-MS/MS) (IA-MS) assay. METHODS IA-MS sample analysis involved the addition of an internal standard, immunoaffinity purification of tau using a tau monoclonal antibody coupled to magnetic beads, trypsin digestion, and quantification of a surrogate tau peptide by LC-MS/MS using a Waters Trizaic nanoTile ultraperformance LC microfluidic device. Further characterization of tau peptides was performed by full-scan MS using a Thermo Orbitrap LC-MS. CSF samples from a cohort of age-matched controls and patients with AD were analyzed by the IA-MS method as well as a commercially available immunoassay. RESULTS The IA-MS assay had intra- and interassay imprecision values of 3.2% to 8.1% CV and 7.8% to 18.9% C, respectively, a mean recovery of 106%, and a limit of quantification of 0.25 pmol/L and was able to quantify tau concentrations in all human specimens tested. The IA-MS assay showed a correlation of R2 = 0.950 against a total-tau immunoassay. In patients with AD, tau was increased approximately 2-fold. CONCLUSIONS Combining immunoaffinity enrichment with microflow LC-MS/MS analysis is an effective approach for the development of a highly selective assay to measure total tau and, potentially, other posttranslationally modified forms of tau in CSF.

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