Cryo-EM structures of lipidic fibrils of amyloid-ß (1-40).
Nat Commun
; 15(1): 1297, 2024 Feb 13.
Article
em En
| MEDLINE
| ID: mdl-38351005
ABSTRACT
Alzheimer's disease (AD) is a progressive and incurable neurodegenerative disease characterized by the extracellular deposition of amyloid plaques. Investigation into the composition of these plaques revealed a high amount of amyloid-ß (Aß) fibrils and a high concentration of lipids, suggesting that fibril-lipid interactions may also be relevant for the pathogenesis of AD. Therefore, we grew Aß40 fibrils in the presence of lipid vesicles and determined their structure by cryo-electron microscopy (cryo-EM) to high resolution. The fold of the major polymorph is similar to the structure of brain-seeded fibrils reported previously. The majority of the lipids are bound to the fibrils, as we show by cryo-EM and NMR spectroscopy. This apparent lipid extraction from vesicles observed here in vitro provides structural insights into potentially disease-relevant fibril-lipid interactions.
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1
Base de dados:
MEDLINE
Assunto principal:
Doenças Neurodegenerativas
/
Doença de Alzheimer
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article