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A Parallel Reaction Monitoring Mass Spectrometric Method for Analysis of Potential CSF Biomarkers for Alzheimer's Disease

Brinkmalm, G; Sjodin, S; Simonsen, AH; Hasselbalch, SG; Zetterberg, H; Brinkmalm, A; Blennow, K; (2018) A Parallel Reaction Monitoring Mass Spectrometric Method for Analysis of Potential CSF Biomarkers for Alzheimer's Disease. Proteomics Clinical Applications , 12 (1) , Article 1700131. 10.1002/prca.201700131. Green open access

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Abstract

Scope: The aim of this study was to develop and evaluate a parallel reactionmonitoring mass spectrometry (PRM-MS) assay consisting of a panel ofpotential protein biomarkers in cerebrospinal fluid (CSF).Experimental design: Thirteen proteins were selected based on theirassociation with neurodegenerative diseases and involvement in synapticfunction, secretory vesicle function, or innate immune system. CSF sampleswere digested and two to three peptides per protein were quantified usingstable isotope-labeled peptide standards.Results: Coefficients of variation were generally below 15%. Clinicalevaluation was performed on a cohort of 10 patients with Alzheimer’s disease(AD) and 15 healthy subjects. Investigated proteins of the granin familyexhibited the largest difference between the patient groups. Secretogranin-2(p<0.005) and neurosecretory protein VGF (p<0.001) concentrations werelowered in AD. For chromogranin A, two of three peptides had significantlylowered AD concentrations (p<0.01). The concentrations of the synapticproteins neurexin-1 and neuronal pentraxin-1, as well as neurofascin werealso significantly lowered in AD (p<0.05). The other investigated proteins,β2-microglobulin, cystatin C, amyloid precursor protein, lysozyme C,neurexin-2, neurexin-3, and neurocan core protein, were not significantlyaltered.Conclusion and clinical relevance: PRM-MS of protein panels is a valuabletool to evaluate biomarker candidates for neurodegenerative disorders.

Type: Article
Title: A Parallel Reaction Monitoring Mass Spectrometric Method for Analysis of Potential CSF Biomarkers for Alzheimer's Disease
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/prca.201700131
Publisher version: https://doi.org/10.1002/prca.201700131
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Alzheimer's disease, biomarker, cerebrospinal fluid, mass spectrometry, parallel reaction monitoring
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10065862
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