Cryo-EM structures of amyloid-b 42 filaments from human brains

Filament assembly of amyloid-b peptides ending at residue 42 (A beta 42) is a central event in Alzheimer's disease. Here, we report the cryo-electron microscopy (cryo-EM) structures of A beta 42 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 A beta 42 filaments from the brain differ from those of filaments assembled in vitro. By contrast, in App(NL-F) knock-in mice, A beta 42 deposits were made of type II filaments. Knowledge of A beta 42 filament structures from human brains may lead to the development of inhibitors of assembly and improved imaging agents.

Automated summary

Filament assembly of A beta 42 peptides is a central event in Alzheimer's disease. This study provides cryo-EM structures of A beta 42 filaments from human brains, revealing two types of structurally related filaments. Understanding the structures of A beta 42 filaments from human brains may have important implications for the development of assembly inhibitors and improved imaging agents.