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

被引：68

作者：

Donovan, Laura E. ^{[1
]}

Higginbotham, Lenora ^{[1
]}

Dammer, Eric B. ^{[2
]}

Gearing, Marla ^{[3
,4
]}

Rees, Howard D. ^{[1
]}

Xia, Qiangwei ^{[2
]}

Duong, Duc M. ^{[5
,6
]}

Seyfried, Nicholas T. ^{[1
,5
,6
]}

Lah, James J. ^{[1
,3
]}

Levey, Allan I. ^{[1
,3
]}

机构：

[1] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA

[2] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA

[3] Emory Univ, Sch Med, Ctr Neurodegenerat Dis, Atlanta, GA 30322 USA

[4] Emory Univ, Sch Med, Dept Expt Pathol, Atlanta, GA 30322 USA

[5] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA

[6] Emory Univ, Sch Med, Neurosci Prote Core Facil, Atlanta, GA 30322 USA

来源：

PROTEOMICS CLINICAL APPLICATIONS | 2012年 / 6卷 / 3-4期

基金：

美国国家卫生研究院;

关键词：

Alzheimer's disease; Membrane enrichment; Neurodegeneration; MASS-SPECTROMETRY; PHOSPHOPROTEOMIC ANALYSIS; QUANTITATIVE PROTEOMICS; GENETIC ASSOCIATION; UP-REGULATION; EXPRESSION; MOUSE; HEALTH; UCHL1; TAU;

D O I：

10.1002/prca.201100068

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：201 / 211

页数：11

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