Leistner, C, Wilkinson, M, Burgess, A et al. (7 more authors) (2023) The in-tissue molecular architecture of β-amyloid pathology in the mammalian brain. Nature Communications, 14. 2833. ISSN 2041-1723
Abstract
Amyloid plaques composed of Aβ fibrils are a hallmark of Alzheimer’s disease (AD). However, the molecular architecture of amyloid plaques in the context of fresh mammalian brain tissue is unknown. Here, using cryogenic correlated light and electron tomography we report the in situ molecular architecture of Aβ fibrils in the AppNL-G-F familial AD mouse model containing the Arctic mutation and an atomic model of ex vivo purified Arctic Aβ fibrils. We show that in-tissue Aβ fibrils are arranged in a lattice or parallel bundles, and are interdigitated by subcellular compartments, extracellular vesicles, extracellular droplets and extracellular multilamellar bodies. The Arctic Aβ fibril differs significantly from an earlier AppNL-F fibril structure, indicating a striking effect of the Arctic mutation. These structural data also revealed an ensemble of additional fibrillar species, including thin protofilament-like rods and branched fibrils. Together, these results provide a structural model for the dense network architecture that characterises β-amyloid plaque pathology.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Funding Information: | Funder Grant number UKRI (UK Research and Innovation) Not Known Academy of Medical Sciences SBF005/1046 |
Depositing User: | Symplectic Publications |
Date Deposited: | 12 May 2023 09:34 |
Last Modified: | 01 Aug 2023 15:25 |
Status: | Published |
Publisher: | Nature Research |
Identification Number: | 10.1038/s41467-023-38495-5 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:199098 |