Hallmarks of Alzheimer’s Disease (AD) are extracellular amyloid plaques found in the brain tissue of patients died by suffering AD. These plaques are composed mainly of amyloid-b peptide (Ab), composed of 39-43 residues long. According to the amyloid hypothesis, the predominantly followed concept in AD research, the accumulation of Ab in the brain is the primary influence driving AD pathogenesis. In the recent years, more and more findings point to the fact, that monomeric Ab or small oligomers may be a crucial factor in neurodegeneration typical of AD. The direct interaction of the Ab peptide with the lipid membrane causes membrane disruption as well as may effect signaling and metabolic pathways in the brain. We investigated lipid membranes doped with Ab, and fragments of it with different neutron scattering techniques. In SANS experiments we were able to demonstrate a membrane fusogenic activity of Ab and neutron diffraction revealed detailed structural details on the location of Ab fragments in lipid membranes of various compositions. Quasi-elastic neutron scattering (QENS) was used to study dynamical changes induced by the peptide. To observe the lipid dynamics in a large time window from pico- to nanoseconds, the experiments where performed on neutron spectrometers with different energy resolutions. With this, we could discriminate short range intrinsic lipid dynamics and long range diffusion. The lipid diffusion was altered due to amyloid-b interaction and the observed changes differ in the fluid or gel phase, respectively. For example, in membranes doped with the Ab(22-40) fragment the in-plane Brownian diffusion of lipids near the phase transition temperature was slowed down in comparison to the pure membrane.

Modulation of lipid membrane structure and dynamics in the presence of amyloid-ß peptide

253rd National Meeting (2017)

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