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

Amyloid P-peptides (A beta s) 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 A beta s in the brain. Particularly, insulin-degrading enzyme (IDE) has been shown to degrade A beta s at different cleavage sites, but the experimental results reported in the literature and obtained by mass spectrometry methods are somehow fragmentary. The detection of A beta s is often complicated by solubility issues, oxidation artifacts and spontaneous aggregation/cleavage and, in order to rationalize the different reported results, we analyzed A beta s 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 A beta s detection. Finally, cleavage sites produced by interaction of A beta s with IDE are identified, two of which had never been reported in the literature. (C) 2009 Elsevier B.V. All rights reserved.