| First Author | Leistner C | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 2833 |
| PubMed ID | 37198197 | Mgi Jnum | J:341267 |
| Mgi Id | MGI:7483785 | Doi | 10.1038/s41467-023-38495-5 |
| Citation | Leistner C, et al. (2023) The in-tissue molecular architecture of beta-amyloid pathology in the mammalian brain. Nat Commun 14(1):2833 |
| abstractText | Amyloid plaques composed of Abeta 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 Abeta fibrils in the App(NL-G-F) familial AD mouse model containing the Arctic mutation and an atomic model of ex vivo purified Arctic Abeta fibrils. We show that in-tissue Abeta 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 Abeta fibril differs significantly from an earlier App(NL-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 beta-amyloid plaque pathology. |
