(221g) Β-Amyloid Assemblage-Lipid Interactions

Alzheimer's disease is the most common cause of dementia and is widely believed to be due to the accumulation of β-amyloid peptides (Aβ) and their interaction with the cell membrane. Aβ's are hydrophobic peptides derived from the amyloid precursor proteins (APP) by proteolytic cleavage. After cleavage, these peptides are involved in a self-assembly triggered conformational change. They are transformed into structures that bind to the cell membrane, causing cellular degeneration. However, it is not clear how these peptide assemblages disrupt the structural and functional integrity of the membrane. Membrane fluidity is one of the important parameters involved in pathophysiology of disease affected cells. Probing the Aβ aggregate-lipid interactions will help us understand these processes with structural detail. The systems studied were both lipid monolayers and bilayers. Using a variety of techniques, we illuminate the different interactions between the lipids and the Aβ aggregates, attacking the problem from different angles. We show that a fluid lipid monolayer develop immobile domains upon interaction with Aβ aggregates using fluorescence microscopy. Atomic Force Microscopy and Transmission Electron Microscope images indicate that peptide fibrils are fragmented into to smaller nano-assemblages when interacting with the membrane lipids.