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-Structure paper
Title | The in-tissue molecular architecture of β-amyloid pathology in the mammalian brain. |
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Journal, issue, pages | Nat Commun, Vol. 14, Issue 1, Page 2833, Year 2023 |
Publish date | May 17, 2023 |
Authors | Conny Leistner / Martin Wilkinson / Ailidh Burgess / Megan Lovatt / Stanley Goodbody / Yong Xu / Susan Deuchars / Sheena E Radford / Neil A Ranson / René A W Frank / |
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. ...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. |
External links | Nat Commun / PubMed:37198197 / PubMed Central |
Methods | EM (helical sym.) / EM (tomography) |
Resolution | 3.0 - 3.2 Å |
Structure data | EMDB-16018, PDB-8bfa: EMDB-16019, PDB-8bfb: EMDB-18301: In-tissue cryo electron tomograms of App^NL-G-F amyloid plaques |
Source |
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Keywords | PROTEIN FIBRIL / Amyloid / fibril / helical / cross-beta / beta amyloid / ex vivo / arctic mutant / alzheimers disease |