Proteome Sci. 2014 Jan 17;12(1):5. doi: 10.1186/1477-5956-12-5.
Plasma protein profiling of Mild Cognitive Impairment and Alzheimer's disease using iTRAQ quantitative proteomics.
Proteome science
Fei Song, Anne Poljak, Nicole A Kochan, Mark Raftery, Henry Brodaty, George A Smythe, Perminder S Sachdev
PMID: 24433274
PMCID: PMC3898732 DOI: 10.1186/1477-5956-12-5
Abstract
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.
References
- J Cell Mol Med. 2009 Sep;13(9A):2911-25 - PubMed
- Biochemistry. 2002 Dec 10;41(49):14532-8 - PubMed
- Dement Geriatr Cogn Disord. 1998;9 Suppl 2:20-6 - PubMed
- Consult Pharm. 2010 Jul;25(7):440-50 - PubMed
- Mol Immunol. 2008 Aug;45(13):3649-60 - PubMed
- Mol Immunol. 2004 Jan;40(11):785-93 - PubMed
- Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21812-7 - PubMed
- Expert Opin Ther Targets. 2010 Jun;14(6):585-92 - PubMed
- Prenat Diagn. 2008 Aug;28(8):691-8 - PubMed
- J Alzheimers Dis. 2012;28(2):369-75 - PubMed
- Int Psychogeriatr. 2010 Dec;22(8):1248-64 - PubMed
- Arch Neurol. 2010 Jul;67(7):819-25 - PubMed
- Brain. 2006 Nov;129(Pt 11):3042-50 - PubMed
- N Engl J Med. 1997 Apr 24;336(17):1216-22 - PubMed
- Neurol Clin. 2007 Aug;25(3):577-609, v - PubMed
- Nat Med. 2007 Nov;13(11):1359-62 - PubMed
- Biogerontology. 2008 Dec;9(6):381-9 - PubMed
- Arch Neurol. 2010 Jul;67(7):867-72 - PubMed
- Prog Neurobiol. 2013 Feb-Mar;101-102:1-17 - PubMed
- PLoS One. 2012;7(6):e34078 - PubMed
- J Biol Chem. 2010 Nov 19;285(47):36958-68 - PubMed
- Proteomics Clin Appl. 2007 May;1(5):506-12 - PubMed
- J Intern Med. 2004 Sep;256(3):183-94 - PubMed
- JAMA. 2002 Jun 26;287(24):3223-9 - PubMed
- Nat Genet. 2009 Oct;41(10):1088-93 - PubMed
- World Psychiatry. 2008;7(2):72-8 - PubMed
- Springer Semin Immunopathol. 2005 Mar;26(4):485-503 - PubMed
- Nat Protoc. 2009;4(1):44-57 - PubMed
- J Proteome Res. 2008 Jul;7(7):2952-8 - PubMed
- Proteomics. 2004 Jan;4(1):244-56 - PubMed
- J Proteome Res. 2005 May-Jun;4(3):889-99 - PubMed
- J Proteome Res. 2010 Feb 5;9(2):653-63 - PubMed
- J Neurosci. 2004 Jul 14;24(28):6277-82 - PubMed
- Neurobiol Aging. 2004 Sep;25(8):1023-32 - PubMed
- J Biol Chem. 2011 Sep 2;286(35):30314-30323 - PubMed
- Int Immunopharmacol. 2007 Dec 20;7(14):1888-99 - PubMed
- Arch Neurol. 2002 Jun;59(6):972-6 - PubMed
- JAMA. 2002 Jun 26;287(24):3230-7 - PubMed
- Reprod Biomed Online. 2011 Aug;23(2):213-9 - PubMed
- Biochem Soc Trans. 2011 Aug;39(4):898-901 - PubMed
- Nutr Neurosci. 2005 Feb;8(1):21-9 - PubMed
- Brain Res Rev. 2009 Oct;61(2):69-80 - PubMed
- Autoimmun Rev. 2008 May;7(5):391-7 - PubMed
- Neurobiol Aging. 2012 Feb;33(2):433.e11-20 - PubMed
- J Neurochem. 2009 Feb;108(3):707-18 - PubMed
- J Alzheimers Dis. 2010;21(2):585-96 - PubMed
- Proc Natl Acad Sci U S A. 2009 May 5;106(18):7501-6 - PubMed
- Am Fam Physician. 2011 Jun 15;83(12):1425-30 - PubMed
- Biol Psychiatry. 2003 Jul 15;54(2):136-41 - PubMed
- J Proteome Res. 2010 Jan;9(1):352-8 - PubMed
- Clin Chim Acta. 1995 Aug 14;239(2):209-11 - PubMed
- Proteomics. 2010 Apr;10(8):1621-33 - PubMed
- J Neurosci Res. 2011 Apr;89(4):576-84 - PubMed
- Autoimmun Rev. 2008 Jun;7(6):415-20 - PubMed
- Nucleic Acids Res. 2009 Jan;37(1):1-13 - PubMed
- Neurology. 1984 Jul;34(7):939-44 - PubMed
- Mol Neurodegener. 2011 Nov 23;6:79 - PubMed
- Int J Clin Pract. 2008 Jul;62(7):1070-5 - PubMed
- Clin Cancer Res. 2007 Dec 15;13(24):7370-9 - PubMed
- Biochem Biophys Res Commun. 2009 Feb 6;379(2):267-71 - PubMed
- Exp Gerontol. 2002 Jul;37(7):943-8 - PubMed
- Br J Nutr. 2010 Mar;103(5):652-62 - PubMed
- Biochem Biophys Res Commun. 1992 Jul 15;186(1):461-6 - PubMed
- Neurobiol Dis. 2005 Nov;20(2):574-82 - PubMed
- J Intern Med. 2004 Sep;256(3):240-6 - PubMed
- Proteomics Clin Appl. 2008 Apr;2(4):467-77 - PubMed
- Stroke. 2005 Dec;36(12):2637-41 - PubMed
- BMC Cancer. 2008 Jan 28;8:25 - PubMed
- Eur J Clin Invest. 2002 May;32(5):360-71 - PubMed
- J Biomed Biotechnol. 2010;2010:952047 - PubMed
- Nutrition. 2001 Oct;17(10):809-14 - PubMed
- J Exp Med. 2007 Aug 6;204(8):1999-2008 - PubMed
- Nucleic Acids Res. 2009 Jan;37(Database issue):D412-6 - PubMed
- Acta Neuropathol. 1995;89(4):356-62 - PubMed
Publication Types