Monitoring the conformational evolution of Abeta oligomers for the discrimination between toxic and non-toxic forms

This work exploited the synchrotron-based UVRR set-up available at the Beamline IUVS for a deep A?(42) oligomer structure characterization at different prefibrillar and fibrillar aggregation stages, in the absence and in the presence of biomimetic membrane. The UV Raman set up allowed to achieve a good sensitivity in the measurement of A? solution at concentration as low as 10^(-5) M. By modulating the excitation wavelength of the radiation it was possible to obtain Raman spectra at different resonance conditions of the aromatic tyrosine amino acid and the amide of the protein. In particular we used 210 nm, 225 nm and 250 nm excitation and observed significant variations in the spectral profile of A? species under investigation. The elaboration and analysis of results are still ongoing and they will give an accurate Raman picture of A? oligomers and fibrils in terms of exposure of aromatic tyrosine to the aqueous solvent as well as abundance in secondary structures (in articular Amide II) in order to obtain the necessary information for the discrimination between two different A? aggregates (one toxic and the other non-toxic to neurons) and between the mechanism of interaction of the two forms with phospholipid membranes.