Effects of Fatty Acids and Phospholipids on Amyloid-β (Aβ) Peptide Aggregation

Abstract

The aggregates of Aβ found in brains of Alzheimer's patients are strongly believed to be the cause for neuronal death and cognitive decline. Among the different forms of Aβ aggregates, smaller aggregates called ‘soluble oligomers’ are increasingly believed to be the primary neurotoxic species responsible for early synaptic dysfunction. Since it is well known that the Aβ aggregation is a nucleation dependant process, it is widely believed that the toxic oligomers are intermediates to fibril formation, or what we call the ‘on-pathway’ products. Although it is true that there may be toxic oligomers along the fibril formation pathway, it is not obligatory that all toxic oligomers must be ‘on-pathway’ intermediates. It is important to understand the pathways because if the oligomers are ‘off-pathway’ products, their half-life can be significantly longer than the ‘on-pathway’ ones that may result in prolonged toxicity to the neuronal cells. Here, we test this hypothesis in the presence of saturated fatty acids and phosphatidylglycerol lipids by varying their carbon chain lengths. We observed that Aβ aggregation can adopt more than one pathway, and the pathway is dictated by Aβ-fatty acid/lipid ratio. Oligomers generated from lipids and fatty acids were isolated and characterized using thioflavin-T (ThT) fluorescence, immunoblotting and atomic force microscopy (AFM). These data are presented and discussed.