Effect of ferric citrate on amyloid-beta peptides behavior.

Amyloid beta (Aβ) 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 Aβ with metal ions. In the last years the interaction between ZnII , CuII , and Aβ was much studied, but between iron and Aβ it is still little known. In this work we determine how three Aβ peptides, present in AD, interact with FeIII -citrate. The three Aβ peptides are: full length Aβ1-42, an isoform truncated at Glutamic acid in position three, Aβ3-42, and its pyroglutamated form AβpE3-42. Conformation and morphology of the three peptides, aggregated with and without FeIII -citrate were studied. Besides, we have determined the strength of the interactions Aβ/FeIII -citrate studying the effect of ethylenediaminetetraacetic acid as chelator. Results reported here demonstrate that FeIII -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 Aβ1-42 compared to that for the truncated peptides.