In vitro investigations of interactions between amyloid beta peptides (1-40, 1-42) structures and substrates with different natures

Published

Conference Paper

Amyloid beta (Aβ) peptides particularly Aβ 1-40 and Aβ 1-42 are the main components of neuritic plaques in Alzheimer's disease (AD) patients. xtracellular plaque formation has been recognized after incessant investigations along with the formation of intracellular tau protein tangles as the hallmarks of AD. From these two hallmarks, 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 (Aβ) is a physiological peptide secreted from neurons under normal conditions, along with other soluble forms cleaved from the amyloid precursor protein (APP). The soluble forms of APP have neuroprotective and neurotrophic functions, while the Aβ is considered as an unwanted by-product of the APP processing. Under normal conditions there is an anabolic/catabolic equilibrium of the Aβ peptide; therefore, it is believed that the formation of the plaque does not take place. On the other hand, the surface of the neurons may play an important role in the adhesion mechanisms of the Aβ 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 imaged on rigid (mica) and soft biomimetic (lipid bilayers on top of a PEG cushion layer drafted onto a silica surface) substrates the Aβ peptide when incubated under three different media conditions, as a result we have identified three different structures that we have consistently with the literature called monomer, oligomer, and fibrils. We have studied the adhesion mechanisms associated with in situ plaque formation. The structure and topography characteristics of the Aβ 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.

Duke Authors

Cited Authors

  • Jimenez, J; Escobar, MJ; Morgan, D; Norma, A

Published Date

  • December 1, 2005

Published In

  • Aiche Annual Meeting, Conference Proceedings

Start / End Page

  • 5305 - 5311

Citation Source

  • Scopus