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

• Published in: Proteomics. Clinical applications Vol. 12; no. 1
• Main Authors: Brinkmalm, Gunnar, Sjödin, Simon, Simonsen, Anja Hviid, Hasselbalch, Steen Gregers, Zetterberg, Henrik, Brinkmalm, Ann, Blennow, Kaj
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.01.2018
• Subjects: Aged; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnosis; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Alzheimer's disease; Amino Acid Sequence; Amyloid precursor protein; biomarker; Biomarkers; Biomarkers - cerebrospinal fluid; C-Reactive Protein - cerebrospinal fluid; C-Reactive Protein - genetics; Case-Control Studies; Cell Adhesion Molecules - cerebrospinal fluid; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules, Neuronal - cerebrospinal fluid; Cell Adhesion Molecules, Neuronal - genetics; Cerebrospinal fluid; Chromatography, Liquid; Chromogranin A - cerebrospinal fluid; Chromogranin A - genetics; Coefficient of variation; Core protein; Cystatin C; Female; Gene Expression; Humans; Immune system; Innate immunity; Lysozyme; Male; Mass spectrometry; Mass spectroscopy; Middle Aged; Monitoring; Nerve Growth Factors - cerebrospinal fluid; Nerve Growth Factors - genetics; Nerve Tissue Proteins - cerebrospinal fluid; Nerve Tissue Proteins - genetics; Neurocan; Neurodegenerative diseases; Neurological diseases; Neurosciences; Neurovetenskaper; parallel reaction monitoring; Pentraxins; Peptide Fragments - cerebrospinal fluid; Peptides; Pilot Projects; Proteins; Proteolysis; Proteomics - methods; Secretogranin II - cerebrospinal fluid; Secretogranin II - genetics; Tandem Mass Spectrometry - methods; mass spectrometry; biomarker; Alzheimer's disease; parallel reaction monitoring; cerebrospinal fluid
• ISSN: 1862-8346; 1862-8354; 1862-8354
• DOI: 10.1002/prca.201700131

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.