FTIR spectroscopic studies on aggregation process of the beta-amyloid 11-28 fragment and its variants.

Aggregation of Abeta peptides is a seminal event in Alzheimer's disease. Detailed understanding of the Abeta assembly process would facilitate the targeting and design of fibrillogenesis inhibitors. Here, conformational studies using FTIR spectroscopy are presented. As a model peptide, the 11-28 fragment of Abeta was used. This model peptide is known to contain the core region responsible for Abeta aggregation. The structural behavior of the peptide during aggregation provoked by the addition of water to Abeta(11-28) solution in hexafluoroisopropanol was compared with the properties of its variants corresponding to natural, clinically relevant mutants at positions 21-23 (A21G, E22K, E22G, E22Q and D23N). The results showed that the aggregation of the peptides proceeds via a helical intermediate, and it is possible that the formation of alpha-helical structures is preceded by creation of 3(10)-helix/3(10)-turn structures.