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Title:
Plasma protein profiling of Mild Cognitive Impairment and Alzheimerās disease using iTRAQ quantitative proteomics | Proteome Science
Description:
Background With the promise of disease modifying treatments, there is a need for more specific diagnosis and prognosis of Alzheimerās 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.
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Keywords {š}
pubmed, article, google, scholar, plasma, proteins, disease, cas, mci, itraq, protein, alzheimers, analysis, cognitive, results, afamin, study, table, apolipoprotein, dysregulated, impairment, biomarkers, central, samples, mild, vitamin, group, chain, ighm, fibrinogen, expression, biological, data, normal, subjects, domain, complement, patients, human, proteomics, full, brain, identified, multiple, western, blot, levels, published, diagnosis, bioinformatics,
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open access article article download pdf variable post-translational modifications hupo-psi modification nomenclature cyclooxygenase-2-positive macrophages infiltrate histidine-rich glycoprotein polymorphism vitamin d-binding protein automatic literature-mining searches mediates alpha-tocopherol transport pigment epithelium-derived factor large gene/protein lists vitamin e-binding properties includes histidine-rich glycoprotein complex multifactorial conditions/diseases n-terminal variable region neuronal growth-promoting factors applied biosystems/mds sciex diffuse amyloid-beta plaques web-based bioinformatics tools leaky bloodābrain barrier important fat-soluble antioxidant enzyme inhibitor activity large population-based studies c18 pre-column cartridge plasma protein profiling genome-wide association discovery-based proteomics method c4b-binding protein proteome-based plasma biomarkers mu heavy chain full homosapiens genome tandem mass spectrometry cognitive impairment profiles nincds-adrda work group ig heavy chain protein-protein associations article song itraq replicate experiments privacy choices/manage cookies voegele af histidine-rich glycoprotein 10Ā mm tris/hcl phĀ 7 western blot analysis hp1090 hplc system tandem mass spectra american psychiatric association authorsā original file natural human antibodies ms/ms analysis identical heavy chains
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- Li X, Buxbaum JN: Transthyretin and the brain re-visited: is neuronal synthesis of transthyretin protective in Alzheimerās disease?
- Pogge E: Vitamin D and Alzheimerās disease: is there a link?
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headline:Plasma protein profiling of Mild Cognitive Impairment and Alzheimerās disease using iTRAQ quantitative proteomics
description:With the promise of disease modifying treatments, there is a need for more specific diagnosis and prognosis of Alzheimerās 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. 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, 19Ā 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). 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. 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.
datePublished:2014-01-17T00:00:00Z
dateModified:2014-01-17T00:00:00Z
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Biomarkers
Isobaric tags for relative and absolute quantitation (iTRAQ)
Plasma
Mild Cognitive Impairment
Alzheimerās disease
Proteomics
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headline:Plasma protein profiling of Mild Cognitive Impairment and Alzheimerās disease using iTRAQ quantitative proteomics
description:With the promise of disease modifying treatments, there is a need for more specific diagnosis and prognosis of Alzheimerās 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. 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, 19Ā 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). 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. 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.
datePublished:2014-01-17T00:00:00Z
dateModified:2014-01-17T00:00:00Z
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Biomarkers
Isobaric tags for relative and absolute quantitation (iTRAQ)
Plasma
Mild Cognitive Impairment
Alzheimerās disease
Proteomics
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