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bioRxiv · 10.1101/2023.06.28.546947

Cryo-EM structures of lipidic fibrils of amyloid-β (1-40)

Frieg, B.·Han, M.·Giller, K.·Dienemann, C.·Riedel, D.·Becker, S.·Andreas, L. B.·Griesinger, C.·Schröder, G. F.
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Abstract

Alzheimers disease (AD) is a progressive and incurable neurodegenerative disease characterized by the extracellular deposition of amyloid plaques. Investigation into the composition of these plaques revealed a high amount of amyloid-{beta} (A{beta}) fibrils and a high concentration of lipids, suggesting that fibril-lipid interactions may also be relevant for the pathogenesis of AD. Therefore, we grew A{beta}40 fibrils in the presence of lipid vesicles and determined their structure by cryo-electron microscopy (cryo-EM) to high resolution. The fold of the major polymorph is similar to the structure of brain-seeded fibrils reported previously. The majority of the lipids are bound to the fibrils as we show by cryo-EM and NMR spectroscopy. This apparent lipid extraction from vesicles observed here in vitro provides structural insights into potentially disease-relevant fibril-lipid interactions.

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Frieg, B., Han, M., Giller, K., Dienemann, C., Riedel, D., Becker, S., Andreas, L. B., Griesinger, C., Schröder, G. F.. 2023-06-29. Cryo-EM structures of lipidic fibrils of amyloid-β (1-40). https://doi.org/10.1101/2023.06.28.546947

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