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-Structure paper
タイトル | The in-tissue molecular architecture of β-amyloid pathology in the mammalian brain. |
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ジャーナル・号・ページ | Nat Commun, Vol. 14, Issue 1, Page 2833, Year 2023 |
掲載日 | 2023年5月17日 |
著者 | 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 要旨 | 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. |
リンク | Nat Commun / PubMed:37198197 / PubMed Central |
手法 | EM (らせん対称) / EM (トモグラフィー) |
解像度 | 3.0 - 3.2 Å |
構造データ | EMDB-16018, PDB-8bfa: EMDB-16019, PDB-8bfb: EMDB-18301: In-tissue cryo electron tomograms of App^NL-G-F amyloid plaques |
由来 |
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キーワード | PROTEIN FIBRIL / Amyloid (アミロイド) / fibril (フィブリル) / helical / cross-beta / beta amyloid / ex vivo (Ex vivo) / arctic mutant / alzheimers disease |