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A Parallel Reaction Monitoring Mass Spectrometric Method for Analysis of Potential CSF Biomarkers for Alzheimer's Disease
Author(s) -
Brinkmalm Gunnar,
Sjödin Simon,
Simonsen Anja Hviid,
Hasselbalch Steen Gregers,
Zetterberg Henrik,
Brinkmalm Ann,
Blennow Kaj
Publication year - 2018
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.201700131
Subject(s) - biomarker , cystatin c , cerebrospinal fluid , synaptophysin , chemistry , cystatin , alzheimer's disease , chromogranin a , medicine , disease , biochemistry , endocrinology , biology , immunohistochemistry , renal function
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.