Accelerated accumulation of amyloid beta proteins on oxidatively damaged lipid membranes

The fully developed lesion of Alzheimer's Disease is a dense plaque compose d of fibrillar amyloid beta-proteins with a characteristic and well-ordered beta-sheet secondary structure. Because the incipient lesion most likely d evelops when these proteins are first induced to form beta-sheet secondary structure, it is important to understand factors that induce amyloid beta-p roteins to adopt this conformation. In this investigation we used a novel f orm of infrared spectroscopy that can characterize the conformation, orient ation, and rate of accumulation of the protein on various lipid membranes t o determine whether oxidatively damaged phospholipid membranes induce the f ormation of beta-sheet secondary structure in a 42-residue amyloid beta-pro tein. We found that membranes containing oxidatively damaged phospholipids accumulated amyloid beta-protein significantly faster than membranes contai ning only unoxidized or saturated phospholipids. Accelerated accumulation w as also seen when 3 mol % G(M1) ganglioside was incorporated into a saturat ed phosphatidylcholine membrane. The accumulated protein more completely ad opted a beta-sheet conformation on oxidized membranes, and the plane of the beta-sheet was oriented parallel to the plane of the membrane. These resul ts indicate that oxidatively damaged phospholipid membranes promote beta-sh eet formation by amyloid beta-proteins, and they suggest a possible role fo r lipid peroxidation in the pathogenesis of Alzheimer's Disease.