Iron(II) Binding to Amyloid-β, the Alzheimer's Peptide

Iron has been implicated in Alzheimer's disease, but until now no direct proof of Fe-II binding to the amyloid-beta peptide (A beta) has been reported. We used NMR to evidence Fe-II coordination to full-length A beta 40 and truncated A beta 16 peptides at physiological pH and to show that the Fe-II binding site is located in the first 16 amino-acid residues. Fe-II caused selective broadening of some NMR peaks that was dependent on the Fe:A beta stoichiometry and temperature. Analysis of Fe-II broadening effect in the H-1, C-13, and 2D NMR data established that Asp1, Glu3, the three His, but not Tyr10 nor Met35 are the residues mainly involved in Fe-II coordination.