GM₁ Ganglioside Inhibits β‐Amyloid Oligomerization Induced by Sphingomyelin

Abstract β‐Amyloid (Aβ) oligomers are neurotoxic and implicated in Alzheimer's disease. Neuronal plasma membranes may mediate formation of Aβ oligomers in vivo. Membrane components sphingomyelin and GM 1 have been shown to promote aggregation of Aβ; however, these studies were performed under extreme, non‐physiological conditions. We demonstrate that physiological levels of GM 1 , organized in nanodomains do not seed oligomerization of Aβ 40 monomers. We show that sphingomyelin triggers oligomerization of Aβ 40 and that GM 1 is counteractive thus preventing oligomerization. We propose a molecular explanation that is supported by all‐atom molecular dynamics simulations. The preventive role of GM 1 in the oligomerization of Aβ 40 suggests that decreasing levels of GM 1 in the brain, for example, due to aging, could reduce protection against Aβ oligomerization and contribute to the onset of Alzheimer's disease.