Plasma protein profiling of Mild Cognitive Impairment and Alzheimer’s disease using iTRAQ quantitative proteomics

Proteome Science

Perminder S Sachdev²  George A Smythe¹  Henry Brodaty²  Mark Raftery⁴  Nicole A Kochan²  Anne Poljak¹  Fei Song³ 

[1] School of Medical Sciences, University of New South Wales, Sydney, Australia;School of Psychiatry, University of New South Wales, Sydney, Australia;Centre for Healthy Brain Ageing (CHeBA), University of New South Wales, Sydney, Australia;Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, Australia

关键词: Proteomics;    Alzheimer’s disease;    Mild Cognitive Impairment;    Plasma;    Isobaric tags for relative and absolute quantitation (iTRAQ);    Biomarkers;   

Others  :  816675
DOI  :  10.1186/1477-5956-12-5

 received in 2013-08-14, accepted in 2014-01-10,  发布年份 2014

【 摘 要 】

Background

With the promise of disease modifying treatments, there is a need for more specific diagnosis and prognosis of Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Plasma biomarkers are likely to be utilised to increase diagnostic accuracy and specificity of AD and cognitive decline.

Methods

Isobaric tags (iTRAQ) and proteomic methods were used to identify potential plasma biomarkers of MCI and AD. Relative protein expression level changes were quantified in plasma of 411 cognitively normal subjects, 19 AD patients and 261 MCI patients. Plasma was pooled into 4 groups including normal control, AD, amnestic single and multiple domain MCI (aMCI), and nonamnestic single and multiple domain MCI (nMCI). Western-blotting was used to validate iTRAQ data. Integrated function and protein interactions were explored using WEB based bioinformatics tools (DAVID v6.7 and STRING v9.0).

Results

In at least two iTRAQ replicate experiments, 30 proteins were significantly dysregulated in MCI and AD plasma, relative to controls. These proteins included ApoA1, ApoB100, complement C3, C4b-binding protein, afamin, vitamin D-binding protein precursor, isoform 1 of Gelsolin actin regulator, Ig mμ chain C region (IGHM), histidine-rich glycoprotein and fibrinogen β and γ chains. Western-blotting confirmed that afamin was decreased and IGHM was increased in MCI and AD groups. Bioinformatics results indicated that these dysregulated proteins represented a diversity of biological processes, including acute inflammatory response, cholesterol transport and blood coagulation.

Conclusion

These findings demonstrate that expression level changes in multiple proteins are observed in MCI and AD plasma. Some of these, such as afamin and IGHM, may be candidate biomarkers for AD and the predementia condition of MCI.

【 授权许可】

   
2014 Song et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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