MALDI, AP/MALDI and ESI techniques for the MS detection of amyloid β-peptides

Abstract: Amyloid β-peptides (Aβs) are involved in several neuropathological conditions such as Alzheimer''s disease and considerable experimental evidences have emerged indicating that different proteases play a major role in regulating the accumulation of Aβs in the brain. Particularly, insulin-degrading enzyme (IDE) has been shown to degrade Aβs at different cleavage sites, but the experimental results reported in the literature and obtained by mass spectrometry methods are somehow fragmentary. The detection of Aβs is often complicated by solubility issues, oxidation artifacts and spontaneous aggregation/cleavage and, in order to rationalize the different reported results, we analyzed Aβs solutions by three different MS approaches: matrix assisted laser desorption ionization-time of flight (MALDI-TOF), atmospheric pressure (AP) MALDI ion trap and electrospray ionization (ESI) ion trap. Differences in the obtained results are discussed and ESI is chosen as the most suitable MS method for Aβs detection. Finally, cleavage sites produced by interaction of Aβs with IDE are identified, two of which had never been reported in the literature. [Copyright &y& Elsevier]