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

Author

Listed:
  • Benedikt Frieg

    (Forschungszentrum Jülich)

  • Mookyoung Han

    (Max Planck Institute for Multidisciplinary Sciences)

  • Karin Giller

    (Max Planck Institute for Multidisciplinary Sciences)

  • Christian Dienemann

    (Max Planck Institute for Multidisciplinary Sciences)

  • Dietmar Riedel

    (Max-Planck-Institute for Multidisciplinary Sciences)

  • Stefan Becker

    (Max Planck Institute for Multidisciplinary Sciences)

  • Loren B. Andreas

    (Max Planck Institute for Multidisciplinary Sciences)

  • Christian Griesinger

    (Max Planck Institute for Multidisciplinary Sciences
    University of Göttingen)

  • Gunnar F. Schröder

    (Forschungszentrum Jülich
    Heinrich Heine University Düsseldorf)

Abstract

Alzheimer’s 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-β (Aβ) fibrils and a high concentration of lipids, suggesting that fibril-lipid interactions may also be relevant for the pathogenesis of AD. Therefore, we grew Aβ40 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.

Suggested Citation

  • Benedikt Frieg & Mookyoung Han & Karin Giller & Christian Dienemann & Dietmar Riedel & Stefan Becker & Loren B. Andreas & Christian Griesinger & Gunnar F. Schröder, 2024. "Cryo-EM structures of lipidic fibrils of amyloid-β (1-40)," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-43822-x
    DOI: 10.1038/s41467-023-43822-x
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    References listed on IDEAS

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    1. Mathias Jucker & Lary C. Walker, 2013. "Self-propagation of pathogenic protein aggregates in neurodegenerative diseases," Nature, Nature, vol. 501(7465), pages 45-51, September.
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