8BFB

Sarkosyl-extracted AppNL-G-F Abeta42 fibril structure (Methoxy-X04-labelled mice)

Summary for 8BFB

• Entry DOI: 10.2210/pdb8bfb/pdb
• EMDB information: 16019
• Descriptor: Amyloid-beta precursor protein (1 entity in total)
• Functional Keywords: amyloid, fibril, helical, cross-beta, beta amyloid, protein fibril, ex vivo, arctic mutant, alzheimers disease
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 10
• Total formula weight: 44480.25

Authors

Wilkinson, M.,Leistner, C.,Burgess, A.,Goodfellow, S.,Deuchars, S.,Ranson, N.A.,Radford, S.E.,Frank, R.A.W. (deposition date: 2022-10-24, release date: 2023-05-31, Last modification date: 2024-07-24)

Primary citation

Leistner, C.,Wilkinson, M.,Burgess, A.,Lovatt, M.,Goodbody, S.,Xu, Y.,Deuchars, S.,Radford, S.E.,Ranson, N.A.,Frank, R.A.W.
The in-tissue molecular architecture of beta-amyloid pathology in the mammalian brain.
Nat Commun, 14:2833-2833, 2023

PubMed 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 App 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 App 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.

PubMed: 37198197
DOI: 10.1038/s41467-023-38495-5

Experimental method

ELECTRON MICROSCOPY (3.2 Å)