ジャーナル: Nat Commun / 年: 2023 タイトル: The in-tissue molecular architecture of β-amyloid pathology in the mammalian brain. 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 / 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.
装置: OTHER 詳細: 2000 bar. The value given for _em_high_pressure_freezing.instrument is Leica EM ICE. This is not in a list of allowed values {'OTHER', 'EMS-002 RAPID IMMERSION FREEZER', 'LEICA EM PACT2', ...詳細: 2000 bar. The value given for _em_high_pressure_freezing.instrument is Leica EM ICE. This is not in a list of allowed values {'OTHER', 'EMS-002 RAPID IMMERSION FREEZER', 'LEICA EM PACT2', 'LEICA EM HPM100', 'LEICA EM PACT', 'BAL-TEC HPM 010'} so OTHER is written into the XML file.
Cryo protectant
20% Dextran 40000
切片作成
ウルトラミクロトーム - 装置: cryo-ultramicrotome (Leica EM FC7) ウルトラミクロトーム - 温度: 123 K / ウルトラミクロトーム - 最終 厚さ: 100
-
電子顕微鏡法
顕微鏡
FEI TITAN KRIOS
撮影
フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: COUNTING / 平均露光時間: 2.0 sec. / 平均電子線量: 61.0 e/Å2