Effect of ferric citrate on amyloid-beta peptides behavior

Amyloid beta (A) aggregation and oxidative stress are two of the central events in Alzheimer's Disease (AD). Both these phenomena can be caused by the interaction of A with metal ions. In the last years the interaction between Zn-II, Cu-II, and A was much studied, but between iron and A it is still little known. In this work we determine how three A peptides, present in AD, interact with Fe-III-citrate. The three A peptides are: full length A1-42, an isoform truncated at Glutamic acid in position three, A3-42, and its pyroglutamated form ApE3-42. Conformation and morphology of the three peptides, aggregated with and without Fe-III-citrate were studied. Besides, we have determined the strength of the interactions A/Fe-III-citrate studying the effect of ethylenediaminetetraacetic acid as chelator. Results reported here demonstrate that Fe-III-citrate promotes the aggregation in all the three peptides. Moreover, Aspartic acid 1, Glutamic acid 3, and Tyrosine 10 have an important role in the coordination with iron, generating a more stable complex for A1-42 compared to that for the truncated peptides.