Molecular details of aluminium-amyloid β peptide interaction by nuclear magnetic resonance.

Alzheimer's disease (AD) is a devastating neurodegenerative condition that poses major challenges to human health. Both amyloid β (Aβ) and metal ions such as aluminium are implicated in the development of AD. By the means of NMR, the interactions of Al3+ with Aβ1-28 peptide as well as the Aβ1-28 analogues were studied, and the key binding sites of Al3+ in Aβ determined. NMR data showed Al3+ interacts with Aβ1-28 at the NH and αH of numerous residues by exhibiting upfield shifts. Using Aβ analogues where His6, His13 and His14 were individually replaced by alanine residue(s), including Aβ H6A, Aβ H13A, Aβ H14A, and Aβ H6,13,14A, the results demonstrated that the histidine residues (His6, His13 and His14) and N-terminal Asp1 were involved in the Al3+ coordination. These findings provide, for the first time, the details of the molecular interaction between Al3+ and Aβ, which points to the potential role of Al3+ in Aβ aggregation, hence in AD development.