THE USE OF MASS SPECTROMETRY TO STUDY AMYLOID-beta PEPTIDES

Amyloid-beta peptide (A beta) varies in size from 39 to 43 amino acids and arises from sequential beta- and gamma-secretase processing of the amyloid precursor protein. Whereas the non-pathological role for A beta is yet to be established, there is no disputing that A beta is now widely regarded as central to the development of Alzheimer's disease (AD). The so named "amyloid cascade hypothesis" states that disease progression is the result of an increased A beta burden in affected areas of the brain. To elucidate the Ab role in AD, many analytical approaches have been proposed as suitable tools to investigate not only the total A beta load but also many other issues that are considered crucial for AD, such as: (i) the aggregation state in which A beta is present; (ii) its interaction with other species or metals; (iii) its ability to induce oxidative stress; and (iv) its degradative pathways. This review provides an insight into the use of mass spectrometry (MS) in the field of A beta investigation aimed to assess its role in AD. In particular, the different MS-based approaches applied in vitro and in vivo that can provide detailed information on the above-mentioned issues are reviewed. Moreover, the advantages offered by the MS methods over all the other techniques are highlighted, together with the recent developments and uses of combined analytical approaches to detect and characterize A beta. (C) 2010 Wiley Periodicals, Inc., Mass Spec Rev 30:347-365, 2011