8-plex quantitation of changes in cerebrospinal fluid protein expression in subjects undergoing intravenous immunoglobulin treatment for Alzheimer's disease

Choe, L., D'Ascenzo, M., Relkin, N. R., Pappin, D., Ross, P., Williamson, B., Guertin, S., Pribil, P., Lee, K. H. (October 2007) 8-plex quantitation of changes in cerebrospinal fluid protein expression in subjects undergoing intravenous immunoglobulin treatment for Alzheimer's disease. Proteomics, 7 (20). pp. 3651-60. ISSN 1615-9853 (Print)1615-9853 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/17880003
DOI: 10.1002/pmic.200700316

Abstract

An 8-plex version of an isobaric reagent for the quantitation of proteins using shotgun methods is presented. The 8-plex version of the reagent relies on amine-labeling chemistry of peptides similar to 4-plex reagents. MS/MS reporter ions at 113, 114, 115, 116, 117, 118, 119, and 121 m/z are used to quantify protein expression. This technology which was first applied to a test mixture consisting of eight proteins and resulted in accurate quantitation, has the potential to increase throughput of analysis for quantitative shotgun proteomics experiments when compared to 2- and 4-plex methods. The technology was subsequently applied to a longitudinal study of cerebrospinal fluid (CSF) proteins from subjects undergoing intravenous Ig treatment for Alzheimer's disease. Results from this study identify a number of protein expression changes that occur in CSF after 3 and 6 months of treatment compared to a baseline and compared to a drug washout period. A visualization tool was developed for this dataset and is presented. The tool can aid in the identification of key peptides and measurements. One conclusion aided by the visualization tool is that there are differences in considering peptide-based observations versus protein-based observations from quantitative shotgun proteomics studies.

Item Type: Paper
Uncontrolled Keywords: Alzheimer Disease/ cerebrospinal fluid/immunology/ therapy Amino Acid Sequence Carbonic Anhydrases/biosynthesis/cerebrospinal fluid/genetics Cerebrospinal Fluid Proteins/ analysis/ biosynthesis/genetics Gene Expression Regulation/immunology Humans Immunoglobulins, Intravenous/administration & dosage/ therapeutic use Indicators and Reagents Infusions, Intravenous Mass Spectrometry Molecular Sequence Data Proteomics/instrumentation/methods
Subjects: diseases & disorders > mental disorders > delirium dementia cognitive disorders > Alzheimer's disease
diseases & disorders > mental disorders > delirium dementia cognitive disorders
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
Investigative techniques and equipment
diseases & disorders > mental disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
Investigative techniques and equipment > spectroscopy > mass spectrometry
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein characterization
Investigative techniques and equipment > spectroscopy
CSHL Authors:
Communities: CSHL labs > Pappin lab
Depositing User: Matt Covey
Date: October 2007
Date Deposited: 01 Mar 2013 14:21
Last Modified: 01 Mar 2013 14:21
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27642

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