The role of lipids and the lipid membrane in interacting and altering the assembly pathways for formation of Alzheimer’s Aβ aggregates is well recognized. However, gangliosides, amphipathic lipids that are exclusive and abundant in mammalian brain, have been reported to show specific effects in the formation of plaques and aggregates associated with the disease. In this study, we employ molecular dynamics to examine the possibly pathways for interaction between Aβ monomers in the absence and presence of the GM1ganglioside. We construct potentials of mean force between complexes of lipid and peptide to examine the free energy driving forces that enhance the solubility of small oligomeric states of Aβ in the presence of GM1 and provide some microscopic rational for the observed delay and inhibition of aggregation kinetics in Alzheimer’s Aβ peptides in solution with GM1 below its critical micellar concentration.

Exploring the role of amphiphilic soluble lipids on Alzheimer’s Aβ aggregation

ACS Spring 2022

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