Nano-infrared analysis of amyloid β1–42 fibrils formed in the presence of lipids with unsaturated fatty acids

Abstract

Alzheimer's disease (AD) is characterized by progressive memory loss and serious impairment of cognitive abilities. AD is the most common cause of dementia, affecting more than 44 million people around the world. The hallmark of AD is amyloid plaques, extracellular deposits primarily found in the frontal lobe, that are composed of amyloid β (Aβ) aggregates. In this study, we utilized nano-infrared spectroscopy, also known as Atomic Force Microscopy Infrared (AFM-IR) spectroscopy to investigate the effect of unsaturated phospholipids on the rate of Aβ_1–42 aggregation. We found that unsaturated phosphatidylcholine, phosphatidylserine, and cardiolipin strongly suppressed aggregation of Aβ_1–42. Furthermore, Aβ_1–42 fibrils formed in the presence of such lipids exerted significantly lower cell toxicity compared to the protein aggregates formed in the lipid-free environment. These findings suggest that dietary changes linked to the increased consumption of unsaturated phospholipids could be considered as a potential therapeutic approach that can decelerate the progression of AD. These results also suggest that large unilamellar vesicles with unsaturated lipids can be used as potential therapeutics to delay the onset and decelerate the progression of AD.