title: Label-free quantitative LC-MS proteomics of Alzheimer's disease and normally aged human brains.
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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, §Department of Biochemistry and Molecular Biology, ⊥Department of Epidemiology and Public Health, ▽Division of Neuroscience, and ○Department of Human Genetics and Genomics, University of Miami Miller School of Medicine , Miami, Florida, United States.
authors.forename: Victor P
authors.initials: VP
authors.lastname: Andreev
authors.forename: Vladislav A
authors.initials: VA
authors.lastname: Petyuk
authors.forename: Heather M
authors.initials: HM
authors.lastname: Brewer
authors.forename: Yuliya V
authors.initials: YV
authors.lastname: Karpievitch
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.forename: Jennifer
authors.initials: J
authors.lastname: Clarke
authors.forename: David
authors.initials: D
authors.lastname: Camp
authors.forename: Richard D
authors.initials: RD
authors.lastname: Smith
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Lieberman
authors.forename: Roger L
authors.initials: RL
authors.lastname: Albin
authors.forename: Zafar
authors.initials: Z
authors.lastname: Nawaz
authors.forename: Jimmy
authors.initials: J
authors.lastname: El Hokayem
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Myers
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D020543:Proteome / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D040901:Proteomics; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry; D014157:Transcription Factors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D020543:Proteome; D014157:Transcription Factors