posted on 2023-12-05, 10:30authored byJing Hu, Sara Linse, Emma Sparr
Amyloid β peptide
(Aβ) is the crucial protein
component
of extracellular plaques in Alzheimer’s disease. The plaques
also contain gangliosides lipids, which are abundant in membranes
of neuronal cells and in cell-derived vesicles and exosomes. When
present at concentrations above its critical micelle concentration
(cmc), gangliosides can occur as mixed micelles. Here, we study the
coassembly of the ganglioside GM1 and the Aβ peptides Aβ40
and 42 by means of microfluidic diffusional sizing, confocal microscopy,
and cryogenic transmission electron microscopy. We also study the
effects of lipid–peptide interactions on the amyloid aggregation
process by fluorescence spectroscopy. Our results reveal coassembly
of GM1 lipids with both Aβ monomers and Aβ fibrils. The
results of the nonseeded kinetics experiments show that Aβ40
aggregation is delayed with increasing GM1 concentration, while that
of Aβ42 is accelerated. In seeded aggregation reactions, the
addition of GM1 leads to a retardation of the aggregation process
of both peptides. Thus, while the effect on nucleation differs between
the two peptides, GM1 may inhibit the elongation of both types of
fibrils. These results shed light on glycolipid–peptide interactions
that may play an important role in Alzheimer’s pathology.