Investigation of Liposome Effects on Aggregation of the Amyloid-&beta Peptide Involved in Alzheimer's Disease

Alzheimer's disease (AD) is a form of dementia associated with the buildup of protein plaques in and around brain cells. One major component of these plaques is the fibrillar form of the amyloid-Β protein (AΒ). AΒ monomer is inert, but it becomes a neurotoxin as it aggregates into fibrils. In fact, plaques have been identified as areas of localized toxicity. Increasing evidence suggests that AΒ aggregation can be initiated by contact with lipid bilayers, which comprise cell membranes. Thus, the focus of this study was determine the effect of lipids on AΒ monomer aggregation. 1-Palmitoyl-2-Oleoyl-sn-Glycero-3-[Phospho-rac-(1-glycerol)] (POPG) was the lipid chosen due to its documented ability to accelerate AΒ monomer aggregation. Liposomes were created as model cell membranes and an assay to accurately quantify lipids that comprise these liposomes was developed. Experiments were conducted to study the rate of aggregation of varying concentrations of AΒ and POPG liposomes, to identify the amount of lipid required for optimal AΒ monomer aggregation. Results indicate that an optimal liposome concentration for acceleration of AΒ monomer aggregation exists at each AΒ concentration. Also, the rate of aggregation increases as the concentration of AΒ monomer increases in the presence of a constant liposome concentration. Clearly, understanding AΒ-lipid interactions plays a vital role in uncovering invivo factors that promote AΒ aggregation and, ultimately, the cause of AD.