Aluminum-triggered structural modifications and aggregation of beta-amyloids.

We investigated the structural effects induced by Al3+ on different b-amyloid (Ab) fragments at pH 7.4 and T= 25°C, with particular attention given to the sequences 1-40 and 1-42. Al3+ caused peptide enrichment in b sheet structure and formation of solvent-exposed hydrophobic clusters. These intermediates evolved to polymeric aggregates which organized in fibrillar forms in the case of the Al3+-Ab(1-42) complex. Comparative studies showed that Zn2+ and Cu2+ were much less efficient than Al3+ in stimulating the spontaneous aggregation/fibrillogenesis of Abs. Studies with liposomes as membrane models showed dramatic changes in the structural properties of the lipid bilayer in the presence of Al3+-Ab complexes, suggesting a major role of Al3+ in Ab-induced cell dysfunction. Al3+ effects were abolished by desferrioxamine mesylate (DFO) only in solution. We concluded that, in vivo, DFO may act as a protective agent by preventing or reverting Ab aggregation in the extracellular spaces.