eprintid: 10065862
rev_number: 25
eprint_status: archive
userid: 608
dir: disk0/10/06/58/62
datestamp: 2019-01-15 10:56:49
lastmod: 2021-09-19 22:17:39
status_changed: 2019-01-15 15:44:19
type: article
metadata_visibility: show
creators_name: Brinkmalm, G
creators_name: Sjodin, S
creators_name: Simonsen, AH
creators_name: Hasselbalch, SG
creators_name: Zetterberg, H
creators_name: Brinkmalm, A
creators_name: Blennow, K
title: A Parallel Reaction Monitoring Mass Spectrometric Method for Analysis of Potential CSF Biomarkers for Alzheimer's Disease
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F86
keywords: Alzheimer's disease, biomarker, cerebrospinal fluid, mass spectrometry, parallel reaction monitoring
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
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.
date: 2018-01
date_type: published
publisher: WILEY-V C H VERLAG GMBH
official_url: https://doi.org/10.1002/prca.201700131
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1453048
doi: 10.1002/prca.201700131
lyricists_name: Zetterberg, Henrik
lyricists_id: HZETT94
actors_name: Zetterberg, Henrik
actors_name: Harriot, Anne-Marie
actors_id: HZETT94
actors_id: AHARA72
actors_role: owner
actors_role: impersonator
full_text_status: public
publication: Proteomics Clinical Applications
volume: 12
number: 1
article_number: 1700131
pages: 13
issn: 1862-8354
citation:        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 <https://doi.org/10.1002/prca.201700131>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10065862/1/Zetterberg_Brinkmalm.pdf