National Institutes of Health/National Institute on Aging (NIH/NIA)
P30-AG010133
United Kingdom
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
U01-NS110437
United Kingdom
National Institutes of Health/National Institute on Aging (NIH/NIA)
RF1-AG071177
United Kingdom
Citation
Journal: Science / Year: 2022 Title: Cryo-EM structures of amyloid-β 42 filaments from human brains. Authors: Yang Yang / Diana Arseni / Wenjuan Zhang / Melissa Huang / Sofia Lövestam / Manuel Schweighauser / Abhay Kotecha / Alexey G Murzin / Sew Y Peak-Chew / Jennifer Macdonald / Isabelle Lavenir ...Authors: Yang Yang / Diana Arseni / Wenjuan Zhang / Melissa Huang / Sofia Lövestam / Manuel Schweighauser / Abhay Kotecha / Alexey G Murzin / Sew Y Peak-Chew / Jennifer Macdonald / Isabelle Lavenir / Holly J Garringer / Ellen Gelpi / Kathy L Newell / Gabor G Kovacs / Ruben Vidal / Bernardino Ghetti / Benjamin Ryskeldi-Falcon / Sjors H W Scheres / Michel Goedert / Abstract: Filament assembly of amyloid-β peptides ending at residue 42 (Aβ42) is a central event in Alzheimer’s disease. Here, we report the cryo–electron microscopy (cryo-EM) structures of Aβ42 ...Filament assembly of amyloid-β peptides ending at residue 42 (Aβ42) is a central event in Alzheimer’s disease. Here, we report the cryo–electron microscopy (cryo-EM) structures of Aβ42 filaments from human brains. Two structurally related S-shaped protofilament folds give rise to two types of filaments. Type I filaments were found mostly in the brains of individuals with sporadic Alzheimer’s disease, and type II filaments were found in individuals with familial Alzheimer’s disease and other conditions. The structures of Aβ42 filaments from the brain differ from those of filaments assembled in vitro. By contrast, in knock-in mice, Aβ42 deposits were made of type II filaments. Knowledge of Aβ42 filament structures from human brains may lead to the development of inhibitors of assembly and improved imaging agents.
History
Deposition
Oct 30, 2021
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Header (metadata) release
Nov 24, 2021
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Map release
Nov 24, 2021
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Update
Mar 8, 2023
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Current status
Mar 8, 2023
Processing site: PDBe / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
EMPIAR-10916 (Title: Single particle cryo-EM dataset of sarkosyl-insoluble fraction from the frontal cortex of an individual with Alzheimer’s disease of amyloid-β 42 filaments Data size: 200.7 Data #1: Unaligned multi-frame movies [micrographs - multiframe])
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