Analysis of a membrane-enriched proteome from postmortem human brain tissue in Alzheimer's disease

Authors

  • Laura E. Donovan,

    1. Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA
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  • Lenora Higginbotham,

    1. Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA
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  • Eric B. Dammer,

    1. Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA
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  • Marla Gearing,

    1. Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia, USA
    2. Department of Experimental Pathology, Emory University School of Medicine, Atlanta, Georgia, USA
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  • Howard D. Rees,

    1. Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA
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  • Qiangwei Xia,

    1. Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA
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  • Duc M. Duong,

    1. Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA
    2. Neuroscience Proteomics Core Facility, Emory University School of Medicine, Atlanta, Georgia, USA
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  • Nicholas T. Seyfried,

    1. Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA
    2. Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA
    3. Neuroscience Proteomics Core Facility, Emory University School of Medicine, Atlanta, Georgia, USA
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  • James J. Lah,

    1. Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA
    2. Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia, USA
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  • Allan I. Levey

    1. Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA
    2. Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia, USA
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  • Colour Online: See the article online to view Fig. 2 in colour.

Correspondence: Dr. Nicholas T. Seyfried, Departments of Neurology, Biochemistry, and Neuroscience Proteomics Core Facility, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

E-mail:nseyfri@emory.edu

Fax: +1-404-727-3728

Abstract

Purpose

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.

Experimental design

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.

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