title: Proteomic characterization of postmortem amyloid plaques isolated by laser capture microdissection.
abstract: The presence of amyloid plaques in the brain is one of the pathological hallmarks of Alzheimer's disease (AD). We report here a comprehensive proteomic analysis of senile plaques from postmortem AD brain tissues. Senile plaques labeled with thioflavin-S were procured by laser capture microdissection, and their protein components were analyzed by liquid chromatography coupled with tandem mass spectrometry. We identified a total of 488 proteins co-isolated with the plaques, and we found multiple phosphorylation sites on the neurofilament intermediate chain, implicating the complexity and diversity of cellular processes involved in the plaque formation. More significantly, we identified 26 proteins enriched in the plaques of two AD cases by quantitative comparison with surrounding non-plaque tissues. The localization of several proteins in the plaques was further confirmed by the approach of immunohistochemistry. In addition to previously identified plaque constituents, we discovered novel association of dynein heavy chain with the plaques in human postmortem brain and in a double transgenic AD mouse model, suggesting that neuronal transport may play a role in neuritic degeneration. Overall, our results revealed for the first time the sub-proteome of amyloid plaques that is important for further studies on disease biomarker identification and molecular mechanisms of AD pathogenesis.
authors.affiliation: Department of Human Genetics, Center for Neurodegenerative Disease, Enory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Lujian
authors.initials: L
authors.lastname: Liao
authors.forename: Dongmei
authors.initials: D
authors.lastname: Cheng
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Duc M
authors.initials: DM
authors.lastname: Duong
authors.forename: Tatyana G
authors.initials: TG
authors.lastname: Losik
authors.forename: Marla
authors.initials: M
authors.lastname: Gearing
authors.forename: Howard D
authors.initials: HD
authors.lastname: Rees
authors.forename: James J
authors.initials: JJ
authors.lastname: Lah
authors.forename: Allan I
authors.initials: AI
authors.lastname: Levey
authors.forename: Junmin
authors.initials: J
authors.lastname: Peng
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism; D000682:Amyloid / Q000737:chemistry*; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D015415:Biomarkers; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002853:Chromatography, Liquid; D003593:Cytoplasm / Q000378:metabolism; D019992:Databases as Topic; D004398:Dyneins / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D007834:Lasers; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D010766:Phosphorylation; D010770:Phosphotransferases / Q000737:chemistry; D020543:Proteome; D019076:Transgenes
chemical_list: D000682:Amyloid; D015415:Biomarkers; D020543:Proteome; D010770:Phosphotransferases; D004398:Dyneins