TY  - JOUR
AU  - Frieg, Benedikt
AU  - Han, Mookyoung
AU  - Giller, Karin
AU  - Dienemann, Christian
AU  - Riedel, Dietmar
AU  - Becker, Stefan
AU  - Andreas, Loren B.
AU  - Griesinger, Christian
AU  - Schröder, Gunnar F.
TI  - Cryo-EM structures of lipidic fibrils of amyloid-β (1-40)
JO  - Nature Communications
VL  - 15
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - FZJ-2024-03000
SP  - 1297
PY  - 2024
AB  - 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-β (Aβ) fibrils and a high concentration of lipids, suggesting that fibrillipid interactions may also be relevant for the pathogenesis of AD. Therefore, we grew Aβ40 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.
LB  - PUB:(DE-HGF)16
C6  - 38351005
UR  - <Go to ISI:>//WOS:001161933400016
DO  - DOI:10.1038/s41467-023-43822-x
UR  - https://juser.fz-juelich.de/record/1025606
ER  -