title: Analysis of a membrane-enriched proteome from postmortem human brain tissue in Alzheimer's disease.
abstract: OBJECTIVE
  The present study is a discovery mode proteomics analysis of the membrane-enriched fraction of postmortem brain tissue from Alzheimer's disease (AD) and control cases. This study aims to validate a method to identify new proteins that could be involved in the pathogenesis of AD and potentially serve as disease biomarkers.
  
  
  METHODS
  Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze the membrane-enriched fraction of human postmortem brain tissue from five AD and five control cases of similar age. Biochemical validation of specific targets was performed by immunoblotting.
  
  
  RESULTS
  One thousand seven hundred and nine proteins were identified from the membrane-enriched fraction of frontal cortex. Label-free quantification by spectral counting and G-test analysis identified 13 proteins that were significantly changed in disease. In addition to Tau (MAPT), two additional proteins found to be enriched in AD, ubiquitin carboxy-terminal hydrolase 1 (UCHL1), and syntaxin-binding protein 1 (Munc-18), were validated through immunoblotting. DISCUSSION AND CLINICAL RELEVANCE: Proteomic analysis of the membrane-enriched fraction of postmortem brain tissue identifies proteins biochemically altered in AD. Further analysis of this subproteome may help elucidate mechanisms behind AD pathogenesis and provide new sources of biomarkers.
authors.affiliation: Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Donovan
authors.forename: Lenora
authors.initials: L
authors.lastname: Higginbotham
authors.forename: Eric B
authors.initials: EB
authors.lastname: Dammer
authors.forename: Marla
authors.initials: M
authors.lastname: Gearing
authors.forename: Howard D
authors.initials: HD
authors.lastname: Rees
authors.forename: Qiangwei
authors.initials: Q
authors.lastname: Xia
authors.forename: Duc M
authors.initials: DM
authors.lastname: Duong
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Seyfried
authors.forename: James J
authors.initials: JJ
authors.lastname: Lah
authors.forename: Allan I
authors.initials: AI
authors.lastname: Levey
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000473:pathology*; D001344:Autopsy; D015415:Biomarkers / Q000032:analysis; D001923:Brain Chemistry; D016022:Case-Control Studies; D002462:Cell Membrane / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D051938:Munc18 Proteins / Q000378:metabolism; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D015415:Biomarkers; C054369:MAPT protein, human; D051938:Munc18 Proteins; D020543:Proteome; C497937:STXBP1 protein, human; C482860:UCHL1 protein, human; D016875:tau Proteins; D043222:Ubiquitin Thiolesterase