NMR interaction studies of Ab1-42 with pyroglutamated Abpy3-42

Amyloid peptides, mainly A?1-40 and A?1-42, are the main actors of Alzheimer's disease (AD) . They are the major constituents of the extracellular plaques found in brains of AD patients and are present as extremely toxic soluble oligomers (A?o), in the early stage of the fibrilization process (Nussbaum, 2012). The N-terminus truncated A? peptides show an higher aggregation propensity than full-length peptides and it has been proposed that they initiate amyloid plaque formation (rNussbaum, 2012). The 15-20% of the total truncated A??peptide bears a pyroglutamate residue at the N-terminus (here A?py3-42). In order to investigate the interaction between A?1-42 and A?py3-42 we designed and performed a series of NMR experiments: 1) NMR analysis of A?1-42 self assembling as a function of concentration; 2) titration experiments performed at constant concentration of 15N A?1-42 in the presence of increasing amounts of A?py3-42; 3) titration experiments performed at constant total peptide concentration (15N A?1-42 + A?py3-42) varying, at each point, the concentration of each peptide. Aggregation kinetics was also followed for all the samples by NMR. The results allow to elucidate the complex mechanism of the proposed interaction.