| Literature DB >> 35025654 |
Yang Yang1, Diana Arseni1, Wenjuan Zhang1, Melissa Huang1, Sofia Lövestam1, Manuel Schweighauser1, Abhay Kotecha2, Alexey G Murzin1, Sew Y Peak-Chew1, Jennifer Macdonald1, Isabelle Lavenir1, Holly J Garringer3, Ellen Gelpi4, Kathy L Newell3, Gabor G Kovacs4,5, Ruben Vidal3, Bernardino Ghetti3, Benjamin Ryskeldi-Falcon1, Sjors H W Scheres1, Michel Goedert1.
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 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 AppNL-F 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.Entities:
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Year: 2022 PMID： 35025654 PMCID： PMC7612234 DOI： 10.1126/science.abm7285
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 63.714