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TitleCryo-EM structures of amyloid-β 42 filaments from human brains.
Journal, issue, pagesScience, Vol. 375, Issue 6577, Page 167-172, Year 2022
Publish dateJan 14, 2022
AuthorsYang 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 /
PubMed AbstractFilament 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.
External linksScience / PubMed:35025654 / PubMed Central
MethodsEM (helical sym.)
Resolution2.5 - 3.5 Å
Structure data

13800

7q4b

EMDB-13800, PDB-7q4b:
Type I beta-amyloid 42 Filaments from Human Brain
Method: EM (helical sym.) / Resolution: 2.5 Å

13809

7q4m

EMDB-13809, PDB-7q4m:
Type II beta-amyloid 42 Filaments from Human Brain
Method: EM (helical sym.) / Resolution: 2.8 Å

EMDB-16434: Type Ib beta-amyloid 42 Filaments from Human Brain
Method: EM (helical sym.) / Resolution: 3.5 Å

Chemicals

ChemComp-UNX:
Unknown entry

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
KeywordsPROTEIN FIBRIL / amyloid filaments / Abeta42 / human brain / cryo-EM

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