Lipid membranes induce structural conversion from amyloid oligomers to fibrils

Formation of amyloid oligomers and fibrils underlies the pathogenesis of a number of neurodegenerative diseases such as Alzheimer's. One mechanism of action by which A beta aggregates cause neuronal toxicity is through interactions with cellular membranes. A beta aggregates have been shown to disrupt membrane integrity via pore formation, membrane thinning, or lipid extraction. At the same time, lipid membranes also affect the rate of Ab aggregation and remodel pre-formed A beta fibrils. Here we show that A beta 42 globulomers, a type of well-characterized and stable A beta oligomers, convert to amyloid fibrils in the presence of DOPC liposomes. Electron paramagnetic resonance studies show that the fibrils converted from A beta beta 42 globulomers adopt the same structure as fibrils formed directly from monomers. Our results suggest that the interactions between Ab oligomers and cellular membranes are dynamic. By converting A beta oligomers to fibrils, the lipid membrane can reduce the membrane-disrupting activities caused by these oligomers. Modulation of Ab-membrane interactions as a therapeutic strategy should take into account the dynamic nature of these interactions. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

Formation of amyloid oligomers and fibrils, underlying neurodegenerative diseases like Alzheimer's, involves interactions with cellular membranes. The conversion of Aβ42 globulomers to fibrils in the presence of DOPC liposomes suggests a dynamic nature of interactions between Aβ oligomers and membranes. Lipid membranes can reduce membrane-disrupting activities caused by Aβ oligomers by converting them to fibrils.