The use of mass spectrometry to study amyloid‐β peptides

Abstract

Amyloid-β peptide (Aβ) varies in size from 39 to 43 amino acids and arises from sequential β- and γ-secretase processing of the amyloid precursor protein. Whereas the non-pathological role for Aβ is yet to be established, there is no disputing that Aβ 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 Aβ burden in affected areas of the brain. To elucidate the Aβ role in AD, many analytical approaches have been proposed as suitable tools to investigate not only the total Aβ load but also many other issues that are considered crucial for AD, such as: (i) the aggregation state in which Aβ 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 Aβ 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 Aβ.

Sulforaphane interaction with amyloid beta 1‐40 peptide studied by electrospray ionization mass spectrometry

“…The stock solution of Aβ (100 μM) was prepared in 20 mM (pH 7.4) ammonium acetate buffer and that of SFN (500 μM) in dimethyl sulfoxide. The working solutions of Aβ (10 μM) and SFN (10,20, 30 40 and 50 μM) were prepared by diluting the stock solutions in milli Q water (Merck Millipore, Billerica, MA, USA).…”

Metal ions affect insulin-degrading enzyme activity

“…Indeed, information regarding IDE enzymatic digestions of the full length insulin in the presence of metal ions is very problematic due to insulin aggregation and to the different peptide conformations existing at different peptide/metal ratios [63,64]. As a matter of fact, the ESI/MS characterization of samples containing insulin and metal ions reveals the presence of an insulin-metal interaction, as it is shown in Fig.…”

Mass spectrometry is a multifaceted weapon to be used in the battle against Alzheimer's disease: Amyloid beta peptides and beyond

“…Here, besides an update on the recent studies conducted with MS to monitor and characterize Aβ peptides, we provide an overall discussion on the wider contribution that MS has given to the understanding of the molecular mechanisms involved in AD. Hopefully, the knowledge of the possibilities that MS offers to the scientists who have decided to tackle AD will prompt new findings that eventually might allow us to win the battle against this terrible disease.…”

“…Here, besides an update on the recent studies conducted with MS to monitor and characterize Aβ peptides, 2 we provide an overall discussion on the wider contribution that MS has given to the understanding of the molecular mechanisms involved in AD.…”