Amyloid -Beta Oligomerization in the Presence of Anionic Phospholipids

Low-molecular weight oligomers of amyloid-β (Aβ) peptides have emerged as primary toxic species involved in the Alzheimer disease (AD) pathogenesis. Recent findings suggest that oligomers of distinct conformations could self-propagate toward specific aggregate structures. Regarding the generation of specific oligomer conformers, the association of Aβ with lipids play an important role. In our laboratory, we investigate the role of membrane lipids and surfactants in modulating Ab aggregation to generate distinct oligomer strains. We hypothesize that such strains that vary in biophysical & biochemical properties, could also lead to specific phenotypes in brains. Growing evidence indicate prion-like progression of Ab aggregate seeds that give rise to specific clinicopatholologic phenotypes in the AD. We investigated the characteristics of Aβ oligomers generated in the presence of various ganglioside & anionic phospholipid micelles/liposomes in-vitro. We found that the Aβ peptides interact uniquely with gangliosides and other anionic phospholipids. However, all the oligomers were found to be parallel β-sheet rich with similar molecular weight and hydrodynamic diameter. We also observed distinct range of melting temperatures for all lipid -derived oligomers indicating that they have similar thermodynamic stabilities. Together, these findings indicate that the lipid - derived oligomers may be a part of a distinct class of oligomer strains that could result in a common AD phenotype