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

Gunnar Brinkmalm; Simon Sjödin; Anja Hviid Simonsen; Steen Gregers Hasselbalch; Henrik Zetterberg; Ann Brinkmalm; Kaj Blennow

doi:10.1002/prca.201700131

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

Gunnar Brinkmalm, Simon Sjödin, Anja Hviid Simonsen, Steen Gregers Hasselbalch, Henrik Zetterberg, Ann Brinkmalm, Kaj Blennow

Institut for Klinisk Medicin

43 Citationer (Scopus)

Abstract

Scope: The aim of this study was to develop and evaluate a parallel reaction monitoring mass spectrometry (PRM-MS) assay consisting of a panel of potential protein biomarkers in cerebrospinal fluid (CSF). Experimental design: Thirteen proteins were selected based on their association with neurodegenerative diseases and involvement in synaptic function, secretory vesicle function, or innate immune system. CSF samples were digested and two to three peptides per protein were quantified using stable isotope-labeled peptide standards. Results: Coefficients of variation were generally below 15%. Clinical evaluation was performed on a cohort of 10 patients with Alzheimer's disease (AD) and 15 healthy subjects. Investigated proteins of the granin family exhibited the largest difference between the patient groups. Secretogranin-2 (p<0.005) and neurosecretory protein VGF (p<0.001) concentrations were lowered in AD. For chromogranin A, two of three peptides had significantly lowered AD concentrations (p<0.01). The concentrations of the synaptic proteins neurexin-1 and neuronal pentraxin-1, as well as neurofascin were also 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 significantly altered. Conclusion and clinical relevance: PRM-MS of protein panels is a valuable tool to evaluate biomarker candidates for neurodegenerative disorders.

Originalsprog	Engelsk
Artikelnummer	1700131
Tidsskrift	Proteomics - Clinical Applications
Vol/bind	12
Udgave nummer	1
Antal sider	13
ISSN	1862-8346
DOI	https://doi.org/10.1002/prca.201700131
Status	Udgivet - jan. 2018

Adgang til dokumentet

10.1002/prca.201700131

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/prca.201700131

Citationsformater

@article{843aa7a2c8ba44a480bc2b2309686fef,

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

abstract = "Scope: The aim of this study was to develop and evaluate a parallel reaction monitoring mass spectrometry (PRM-MS) assay consisting of a panel of potential protein biomarkers in cerebrospinal fluid (CSF). Experimental design: Thirteen proteins were selected based on their association with neurodegenerative diseases and involvement in synaptic function, secretory vesicle function, or innate immune system. CSF samples were digested and two to three peptides per protein were quantified using stable isotope-labeled peptide standards. Results: Coefficients of variation were generally below 15%. Clinical evaluation was performed on a cohort of 10 patients with Alzheimer's disease (AD) and 15 healthy subjects. Investigated proteins of the granin family exhibited the largest difference between the patient groups. Secretogranin-2 (p<0.005) and neurosecretory protein VGF (p<0.001) concentrations were lowered in AD. For chromogranin A, two of three peptides had significantly lowered AD concentrations (p<0.01). The concentrations of the synaptic proteins neurexin-1 and neuronal pentraxin-1, as well as neurofascin were also 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 significantly altered. Conclusion and clinical relevance: PRM-MS of protein panels is a valuable tool to evaluate biomarker candidates for neurodegenerative disorders.",

keywords = "Aged, Alzheimer Disease/cerebrospinal fluid, Amino Acid Sequence, Biomarkers/cerebrospinal fluid, C-Reactive Protein/cerebrospinal fluid, Case-Control Studies, Cell Adhesion Molecules/cerebrospinal fluid, Cell Adhesion Molecules, Neuronal/cerebrospinal fluid, Chromatography, Liquid, Chromogranin A/cerebrospinal fluid, Female, Gene Expression, Humans, Male, Middle Aged, Nerve Growth Factors/cerebrospinal fluid, Nerve Tissue Proteins/cerebrospinal fluid, Peptide Fragments/cerebrospinal fluid, Pilot Projects, Proteolysis, Proteomics/methods, Secretogranin II/cerebrospinal fluid, Tandem Mass Spectrometry/methods",

author = "Gunnar Brinkmalm and Simon Sj{\"o}din and Simonsen, {Anja Hviid} and Hasselbalch, {Steen Gregers} and Henrik Zetterberg and Ann Brinkmalm and Kaj Blennow",

note = "{\textcopyright} 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",

year = "2018",

month = jan,

doi = "10.1002/prca.201700131",

language = "English",

volume = "12",

journal = "Proteomics - Clinical Applications",

issn = "1862-8346",

publisher = "Wiley - V C H Verlag GmbH & Co. KGaA",

number = "1",

}

TY - JOUR

T1 - A Parallel Reaction Monitoring Mass Spectrometric Method for Analysis of Potential CSF Biomarkers for Alzheimer's Disease

AU - Brinkmalm, Gunnar

AU - Sjödin, Simon

AU - Simonsen, Anja Hviid

AU - Hasselbalch, Steen Gregers

AU - Zetterberg, Henrik

AU - Brinkmalm, Ann

AU - Blennow, Kaj

PY - 2018/1

Y1 - 2018/1

N2 - Scope: The aim of this study was to develop and evaluate a parallel reaction monitoring mass spectrometry (PRM-MS) assay consisting of a panel of potential protein biomarkers in cerebrospinal fluid (CSF). Experimental design: Thirteen proteins were selected based on their association with neurodegenerative diseases and involvement in synaptic function, secretory vesicle function, or innate immune system. CSF samples were digested and two to three peptides per protein were quantified using stable isotope-labeled peptide standards. Results: Coefficients of variation were generally below 15%. Clinical evaluation was performed on a cohort of 10 patients with Alzheimer's disease (AD) and 15 healthy subjects. Investigated proteins of the granin family exhibited the largest difference between the patient groups. Secretogranin-2 (p<0.005) and neurosecretory protein VGF (p<0.001) concentrations were lowered in AD. For chromogranin A, two of three peptides had significantly lowered AD concentrations (p<0.01). The concentrations of the synaptic proteins neurexin-1 and neuronal pentraxin-1, as well as neurofascin were also 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 significantly altered. Conclusion and clinical relevance: PRM-MS of protein panels is a valuable tool to evaluate biomarker candidates for neurodegenerative disorders.

AB - Scope: The aim of this study was to develop and evaluate a parallel reaction monitoring mass spectrometry (PRM-MS) assay consisting of a panel of potential protein biomarkers in cerebrospinal fluid (CSF). Experimental design: Thirteen proteins were selected based on their association with neurodegenerative diseases and involvement in synaptic function, secretory vesicle function, or innate immune system. CSF samples were digested and two to three peptides per protein were quantified using stable isotope-labeled peptide standards. Results: Coefficients of variation were generally below 15%. Clinical evaluation was performed on a cohort of 10 patients with Alzheimer's disease (AD) and 15 healthy subjects. Investigated proteins of the granin family exhibited the largest difference between the patient groups. Secretogranin-2 (p<0.005) and neurosecretory protein VGF (p<0.001) concentrations were lowered in AD. For chromogranin A, two of three peptides had significantly lowered AD concentrations (p<0.01). The concentrations of the synaptic proteins neurexin-1 and neuronal pentraxin-1, as well as neurofascin were also 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 significantly altered. Conclusion and clinical relevance: PRM-MS of protein panels is a valuable tool to evaluate biomarker candidates for neurodegenerative disorders.

KW - Aged

KW - Alzheimer Disease/cerebrospinal fluid

KW - Amino Acid Sequence

KW - Biomarkers/cerebrospinal fluid

KW - C-Reactive Protein/cerebrospinal fluid

KW - Case-Control Studies

KW - Cell Adhesion Molecules/cerebrospinal fluid

KW - Cell Adhesion Molecules, Neuronal/cerebrospinal fluid

KW - Chromatography, Liquid

KW - Chromogranin A/cerebrospinal fluid

KW - Female

KW - Gene Expression

KW - Humans

KW - Male

KW - Middle Aged

KW - Nerve Growth Factors/cerebrospinal fluid

KW - Nerve Tissue Proteins/cerebrospinal fluid

KW - Peptide Fragments/cerebrospinal fluid

KW - Pilot Projects

KW - Proteolysis

KW - Proteomics/methods

KW - Secretogranin II/cerebrospinal fluid

KW - Tandem Mass Spectrometry/methods

U2 - 10.1002/prca.201700131

DO - 10.1002/prca.201700131

M3 - Journal article

C2 - 29028155

SN - 1862-8346

VL - 12

JO - Proteomics - Clinical Applications

JF - Proteomics - Clinical Applications

IS - 1

M1 - 1700131

ER -

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

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater