Advancing cerebrospinal fluid biomarker discovery by mass spectrometry

2015 ◽  
Vol 5 (5) ◽  
pp. 371-373 ◽  
Author(s):  
Johan Gobom
Keyword(s):  
Mass Spectrometry ◽  
Cerebrospinal Fluid ◽  
Biomarker Discovery ◽  
Fluid Biomarker

Biomarker Discovery by Mass Spectrometry in Cerebrospinal Fluid and Plasma after Global Hypoxia-Ischemia in Newborn Piglets

Neonatology ◽  
2018 ◽  
Vol 114 (4) ◽  
pp. 307-314
Author(s):  
Kasper Jacobsen Kyng ◽  
Anders Valdemar Edhager ◽  
Tine Brink Henriksen ◽  
Christer Zøylner Swan ◽  
Niels Gregersen ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cerebrospinal Fluid ◽  
Biomarker Discovery ◽  
Newborn Piglets ◽  
Hypoxia Ischemia

Application of an End-to-End Biomarker Discovery Platform to Identify Target Engagement Markers in Cerebrospinal Fluid by High Resolution Differential Mass Spectrometry

2010 ◽  
Vol 9 (3) ◽  
pp. 1392-1401 ◽  
Author(s):  
Cloud P. Paweletz ◽  
Matthew C. Wiener ◽  
Andrey Y. Bondarenko ◽  
Nathan A. Yates ◽  
Qinghua Song ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cerebrospinal Fluid ◽  
High Resolution ◽  
Biomarker Discovery ◽  
Target Engagement ◽  
End To End

Chemical profiling of cerebrospinal fluid by multiple reaction monitoring mass spectrometry

The Analyst ◽  
2016 ◽  
Vol 141 (18) ◽  
pp. 5252-5255 ◽  
Author(s):  
Christina R. Ferreira ◽  
Karen E. Yannell ◽  
Brit Mollenhauer ◽  
Ryan D. Espy ◽  
Fernanda B. Cordeiro ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cerebrospinal Fluid ◽  
Biomarker Discovery ◽  
Multiple Reaction Monitoring ◽  
Reaction Monitoring ◽  
Chemical Profiling

We report an accelerated biomarker discovery workflow and results of sample screening by mass spectrometry based on multiple reaction monitoring (MRM).

scholarly journals Tandem mass spectrometry-based identification of protein profiles in the cerebrospinal fluid of Alzheimer’s dementia patients

2021 ◽  
Author(s):  
Anamika Misra ◽  
Sankha Shubhra Chakrabarti ◽  
Indrajeet Singh Gambhir ◽  
Meghraj Singh Baghel ◽  
Yugendra Ramchandra Patil
Keyword(s):  
Mass Spectrometry ◽  
Cerebrospinal Fluid ◽  
Growth Factor ◽  
Tandem Mass Spectrometry ◽  
Biomarker Discovery ◽  
Early Stage ◽  
Enrichment Analysis ◽  
Tandem Mass ◽  
Insulin Like Growth Factor ◽  
Proteomic Approach

Abstract Background: Alzheimer’s disease (AD) is the most common form of dementia and about two thirds cases are diagnosed late due to a long asymptomatic phase. There exists the need for newer biomarkers which can add accuracy to AD diagnosis, detect AD at an early stage, as also lend new pathogenic insights into AD. Recent AD biomarker discovery has focused on proteomic approaches, especially in the cerebrospinal fluid. Methods: We used a bottom-up proteomic approach. Cerebrospinal fluid (CSF) samples from 6 patients with AD and 6 controls were digested with trypsin and analyzed by using LC-MS/MS (tandem mass spectrometry). The peptide data from CSF samples of both AD and control groups was then subjected to bioinformatics analysis with STRING version 11.0. Protein-protein interaction networks were constructed, and enrichment analysis performed.Results: Significant up-regulation of 13 proteins in the CSF was observed in AD cases in comparison to controls, while 30 proteins were down-regulated. APOE and LGALS3BP were the upregulated proteins involved in closed network and the downregulated proteins were F2, PENK, IGF2, APOH, SAA1, AHSG, SPP1 and CD44. APOE, APOH, F2 and PENK shared common involvement in multiple biological processes as evident on enrichment. Regulation of insulin like growth factor involving IGF2, F2, APOE and AHSG and glycosaminoglycan binding involving APOE, APOH, F2, SAA1, and CD44 were major pathways of interest determined on bioinformatic analysis.Conclusion: Our study identified novel tentative biomarkers of AD which included F2, PENK and SAA1, as well as reinforced earlier described biomarkers such as APOE and AHSG. These findings need to be validated in larger sample sizes to evaluate their utility as true biomarkers. Further, the pathways of interest- insulin like growth factor regulation and glycosaminoglycan binding need to be studied further in the context of AD.

Concentrations of non-glucose polyols in serum and cerebrospinal fluid from apparently healthy adults and children.

1984 ◽  
Vol 30 (2) ◽  
pp. 188-191 ◽  
Author(s):  
S Yoshioka ◽  
S Saitoh ◽  
S Seki ◽  
K Seki
Keyword(s):  
Mass Spectrometry ◽  
Cerebrospinal Fluid ◽  
Liquid Chromatography ◽  
Healthy Subjects ◽  
Metabolic Diseases ◽  
Gas Liquid Chromatography ◽  
Liquid Chromatography Mass Spectrometry ◽  
Adults And Children ◽  
Healthy Persons ◽  
Apparently Healthy

Abstract Six non-glucose polyols--mannose, fructose, 1-deoxyglucose, mannitol, glucitol, and inositol--were identified and evaluated in human serum and cerebrospinal fluid by gas-liquid chromatography and by gas-liquid chromatography/mass spectrometry. Concentrations of fructose, mannose, and inositol in the serum of healthy persons or children without metabolic diseases varied with age, as already reported for 1-deoxyglucose. Fructose, inositol, and glucitol concentrations in cerebrospinal fluid significantly exceeded those in serum. The method described here for determining polyols and for evaluating polyol patterns in serum, as well as the resulting data on children and healthy subjects, should be useful in investigations of the clinical and physiological significance of polyols.

scholarly journals Toll-like receptor linked cytokine profiles in cerebrospinal fluid discriminate neurological infection from sterile inflammation

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Simone M Cuff ◽  
Joseph P Merola ◽  
Jason P Twohig ◽  
Matthias Eberl ◽  
William P Gray
Keyword(s):  
Cerebrospinal Fluid ◽  
Clinical Practice ◽  
Inflammatory Response ◽  
Nosocomial Infection ◽  
Pathway Analysis ◽  
Interleukin 6 ◽  
Sterile Inflammation ◽  
Interleukin 17 ◽  
Toll Like Receptor ◽  
Fluid Biomarker

Abstract Rapid determination of an infective aetiology causing neurological inflammation in the cerebrospinal fluid can be challenging in clinical practice. Post-surgical nosocomial infection is difficult to diagnose accurately, as it occurs on a background of altered cerebrospinal fluid composition due to the underlying pathologies and surgical procedures involved. There is additional diagnostic difficulty after external ventricular drain or ventriculoperitoneal shunt surgery, as infection is often caused by pathogens growing as biofilms, which may fail to elicit a significant inflammatory response and are challenging to identify by microbiological culture. Despite much research effort, a single sensitive and specific cerebrospinal fluid biomarker has yet to be defined which reliably distinguishes infective from non-infective inflammation. As a result, many patients with suspected infection are treated empirically with broad-spectrum antibiotics in the absence of definitive diagnostic criteria. To begin to address these issues, we examined cerebrospinal fluid taken at the point of clinical equipoise to diagnose cerebrospinal fluid infection in 14 consecutive neurosurgical patients showing signs of inflammatory complications. Using the guidelines of the Infectious Diseases Society of America, six cases were subsequently characterized as infected and eight as sterile inflammation. Twenty-four contemporaneous patients with idiopathic intracranial hypertension or normal pressure hydrocephalus were included as non-inflamed controls. We measured 182 immune and neurological biomarkers in each sample and used pathway analysis to elucidate the biological underpinnings of any biomarker changes. Increased levels of the inflammatory cytokine interleukin-6 and interleukin-6-related mediators such as oncostatin M were excellent indicators of inflammation. However, interleukin-6 levels alone could not distinguish between bacterially infected and uninfected patients. Within the patient cohort with neurological inflammation, a pattern of raised interleukin-17, interleukin-12p40/p70 and interleukin-23 levels delineated nosocomial bacteriological infection from background neuroinflammation. Pathway analysis showed that the observed immune signatures could be explained through a common generic inflammatory response marked by interleukin-6 in both nosocomial and non-infectious inflammation, overlaid with a toll-like receptor-associated and bacterial peptidoglycan-triggered interleukin-17 pathway response that occurred exclusively during infection. This is the first demonstration of a pathway dependent cerebrospinal fluid biomarker differentiation distinguishing nosocomial infection from background neuroinflammation. It is especially relevant to the commonly encountered pathologies in clinical practice, such as subarachnoid haemorrhage and post-cranial neurosurgery. While requiring confirmation in a larger cohort, the current data indicate the potential utility of cerebrospinal fluid biomarker strategies to identify differential initiation of a common downstream interleukin-6 pathway to diagnose nosocomial infection in this challenging clinical cohort.

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