Label-free quantitative LC-MS proteomics of alzheimer's disease and normally aged human brains

Victor P. Andreev, Vladislav A. Petyuk, Heather M. Brewer, Yuliya V. Karpievitch, Fang Xie, Jennifer Clarke, David Camp, Richard D. Smith, Andrew P. Lieberman, Roger L. Albin, Zafar Nawaz, Jimmy El Hokayem, Amanda J. Myers

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

Quantitative proteomics analysis of cortical samples of 10 Alzheimer's disease (AD) brains versus 10 normally aged brains was performed by following the accurate mass and time tag (AMT) approach with the high resolution LTQ Orbitrap mass spectrometer. More than 1400 proteins were identified and quantitated. A conservative approach of selecting only the consensus results of four normalization methods was suggested and used. A total of 197 proteins were shown to be significantly differentially abundant (p-values <0.05, corrected for multiplicity of testing) in AD versus control brain samples. Thirty-seven of these proteins were reported as differentially abundant or modified in AD in previous proteomics and transcriptomics publications. The rest to the best of our knowledge are new. Mapping of the discovered proteins with bioinformatic tools revealed significant enrichment with differentially abundant proteins of pathways and processes known to be important in AD, including signal transduction, regulation of protein phosphorylation, immune response, cytoskeleton organization, lipid metabolism, energy production, and cell death.

Original languageEnglish (US)
Pages (from-to)3053-3067
Number of pages15
JournalJournal of proteome research
Volume11
Issue number6
DOIs
StatePublished - Jun 1 2012
Externally publishedYes

Keywords

  • Alzheimer s disease
  • bioinformatics
  • brain
  • cortical samples
  • normalization
  • proteomics

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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    Andreev, V. P., Petyuk, V. A., Brewer, H. M., Karpievitch, Y. V., Xie, F., Clarke, J., Camp, D., Smith, R. D., Lieberman, A. P., Albin, R. L., Nawaz, Z., El Hokayem, J., & Myers, A. J. (2012). Label-free quantitative LC-MS proteomics of alzheimer's disease and normally aged human brains. Journal of proteome research, 11(6), 3053-3067. https://doi.org/10.1021/pr3001546