(594i) In Vitro Investigations of Interactions between Amyloid Beta Peptides (1-40, 1-42) Structures and Substrates with Different Natures

The amyloid beta peptide particularly the 40 and 42 amino acid residues are the responsible for plaque formation in Alzheimer's disease (AD) patients. Extra cellular plaque formation has been recognized after incessant investigations along with the formation of intracellular tau protein tangles as the hallmarks of AD. Furthermore, the plaque formation has been linked mostly as a cause of the disease and the tangles mostly as a consequence. Our investigation is focused on studying the formation of AD plaques. The amyloid beta (Aß) is a physiological peptide secreted from neurons under normal conditions, along with other soluble forms cleavaged from the amyloid precursor protein (APP). These soluble forms of APP have neuroprotective and neurotrophic functions, while the Aß is considered an unwanted by-product of the APP processing. Under normal conditions there is an anabolic/catabolic equilibrium of the Aß peptide; therefore, it is believed that the formation of the plaque does not take place. On the other hand, the neurons' surface may play an important role in the adhesion mechanisms of the Aß peptide. Our experiments show that the neuron surfaces along with the media conditions may be the most important causes for progressive formation of plaques. We have incubated rigid supports (mica) and soft biomimetic substrates (lipid bilayers on top of a PEG cushion layer drafted onto a silica surface) with the three different conformations of the Aß peptide (monomeric, oligomeric and fibrils structures) to determine the adhesion mechanisms associated with in situ plaque formation. The structure and topography characteristics of the Aß conformations have been followed with atomic force microscopy (AFM). The kinetics and rates of adhesion have been measured with attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. Our results show the progress of the plaques' formation with time where simple monomers deposit on the substrates and allow the development of oligomeric species. The oligomers then grow into fibril-like structures leading finally to the plaques that eventually are seen to insulate real neurons and stop them from the synapse process. The ultimate outcome of this investigation will contribute to understand, prevent and determine possible mechanisms for removing AD plaques.