Metals are found associated with β-pleated sheets of Aβ42 in vivo and may be involved in their formation. Metal chelation has been proposed as a therapy for Alzheimer's disease on the basis that it may safely dissolve precipitated Aβ peptides. We have followed fibrillisation of Aβ42 in the presence of an additional metal ion (Al(III), Fe(III), Zn(II), Cu(II)) over a period of 32 weeks and we have investigated the dissolution of these aged peptide aggregates in the presence of both desferrioxamine (DFO) and ethylenediaminetetraacetic acid (EDTA). Aβ42 either alone or in the presence of Al(III) or Fe(III) formed β-pleated sheets of plaque-like amyloids which were dissolved upon incubation with either chelator. Zn(II) inhibited whilst Cu(II) prevented the formation of β-pleated sheets of Aβ42 and neither of these influences were affected by incubation of the aged peptide aggregates with either DFO or EDTA. Freshly prepared solutions of Aβ42 either alone or in the presence of added Al(III) or Fe(III) did not form β-pleated amyloid in the presence of DFO when incubated for up to 8 weeks. EDTA did not prevent β-pleated amyloid formation in the same treatments and promoted β-pleated amyloid formation in the presence of either Zn(II) or Cu(II). The presence of significant concentrations of Al(III) and Fe(III) as contaminants of 'Aβ42 only' preparations suggested that both of these metals were involved in either triggering the formation or stabilising the structure of β-pleated amyloid. If the formation of such amyloid is critical to the aetiology of AD then the chelation of Al(III) and Fe(III) may prove to be a protective mechanism whilst the chelation of Cu(II) and Zn(II) without also chelating Al(III) and Fe(III) might actually exacerbate the condition.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.