Capabilities of MS for Analytical Quantitative Determination of the Ratio of [alpha]- and [Beta]Asp7 Isoforms of the Amyloid-[Beta] Peptide in Binary Mixtures

There is strong evidence that the amyloid-β peptide (Aβ) plays a crucial role in the pathogenesis of Alzheimer's disease (AD), a lethal neurodegenerative disorder of the elderly. During pathology development, the peptide as well as its various chemically modified isoforms is accumulated in specific brain tissues as characteristic proteinaceous deposits, the so-called amyloid plaques, which are the pathomorphological mark of AD, although the level of Aβ in the blood is the same for healthy individuals and for AD patients. Earlier, it has been shown that isomerization of aspartate 7, the most abundant post-translational modification of the Aβ peptide, is tightly involved in a set of molecular processes associated with AD progression. Therefore, the isoAsp 7-containing Aβ isomer (isoAβ) is assumed to be a potential biomarker of AD that can be identified in the blood. Here, we present an analytical mass spectrometric method for quantitative determination of the ratio of normal and isomerized Aβ fragments 1-16 in their binary mixtures, and all analytical capabilities, such as accuracy, detection limits, and sensitivity of the presented method, are determined and thoroughly discussed. On the basis of this method, an analytical approach for quantitative determination of this modification in the blood will be developed in further studies. [PUBLICATION ABSTRACT]