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Quantification of Amyloid Precursor Protein Isoforms Using Quantification Concatamer Internal Standard



Junjun J. Chen, Meiyao M. Wang, Illarion V. Turko


It is likely that expression and/or post-translational generation of various protein isoforms can be indicative of initial pathological changes or clarifying of pathology development. However, quantification of individual protein isoforms remains a challenge, because they simultaneously possess common and unique amino acid sequences. Quantification concatamer (QconCAT) internal standards were originally proposed for a large-scale proteome quantification and represent artificial proteins that are concatamers of tryptic peptides for several proteins. We have used this basic approach to develop a QconCAT for quantification of various isoforms of amyloid precursor protein (APP). APP-QconCAT includes tryptic peptides that are common for all isoforms of APP concatenated with those tryptic peptides that are unique for specific APP isoforms. Isotope-labeled APP-QconCAT was expressed, purified, characterized and further used for quantification of total APP, APP695, and amyloid-β (Aβ) in the human frontal cortex from control and severe Alzheimer’s disease donors. The biological implications of our quantitative measurements are discussed. It is also expected that using APP-QconCAT(s) will advance our understanding of biological mechanism by which various APP isoforms involved in the pathogenesis of Alzheimer’s disease.
Analytical Chemistry


multiple reaction monitoring, mass spectrometry, QconCAT, isotope-labeled standard, quantification, Alzheimer's disease


Chen, J. , Wang, M. and Turko, I. (2013), Quantification of Amyloid Precursor Protein Isoforms Using Quantification Concatamer Internal Standard, Analytical Chemistry, [online], (Accessed May 28, 2024)


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Created January 2, 2013, Updated November 10, 2018