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Cryo-EM structure and polymorphism of Aβ amyloid fibrils purified from Alzheimer’s brain tissue

Author

Listed:
  • Marius Kollmer

    (Ulm University)

  • William Close

    (Ulm University)

  • Leonie Funk

    (Ulm University)

  • Jay Rasmussen

    (University of Tübingen
    German Center for Neurodegenerative Diseases
    The University of Queensland)

  • Aref Bsoul

    (Ulm University)

  • Angelika Schierhorn

    (Martin-Luther-University)

  • Matthias Schmidt

    (Ulm University)

  • Christina J. Sigurdson

    (University of California, San Diego)

  • Mathias Jucker

    (University of Tübingen
    German Center for Neurodegenerative Diseases)

  • Marcus Fändrich

    (Ulm University)

Abstract

The formation of Aβ amyloid fibrils is a neuropathological hallmark of Alzheimer’s disease and cerebral amyloid angiopathy. However, the structure of Aβ amyloid fibrils from brain tissue is poorly understood. Here we report the purification of Aβ amyloid fibrils from meningeal Alzheimer’s brain tissue and their structural analysis with cryo-electron microscopy. We show that these fibrils are polymorphic but consist of similarly structured protofilaments. Brain derived Aβ amyloid fibrils are right-hand twisted and their peptide fold differs sharply from previously analyzed Aβ fibrils that were formed in vitro. These data underscore the importance to use patient-derived amyloid fibrils when investigating the structural basis of the disease.

Suggested Citation

  • Marius Kollmer & William Close & Leonie Funk & Jay Rasmussen & Aref Bsoul & Angelika Schierhorn & Matthias Schmidt & Christina J. Sigurdson & Mathias Jucker & Marcus Fändrich, 2019. "Cryo-EM structure and polymorphism of Aβ amyloid fibrils purified from Alzheimer’s brain tissue," Nature Communications, Nature, vol. 10(1), pages 1-8, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12683-8
    DOI: 10.1038/s41467-019-12683-8
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    Cited by:

    1. Maximilian Steinebrei & Julian Baur & Anaviggha Pradhan & Niklas Kupfer & Sebastian Wiese & Ute Hegenbart & Stefan O. Schönland & Matthias Schmidt & Marcus Fändrich, 2023. "Common transthyretin-derived amyloid fibril structures in patients with hereditary ATTR amyloidosis," Nature Communications, Nature, vol. 14(1), pages 1-8, December.

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