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