Cryo-EM structures of amyloid-β 42 filaments from human brains
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
Hi-res view of human Aβ42 filaments Alzheimer’s disease is characterized by a loss of memory and other cognitive functions and the filamentous assembly of Aβ and tau in the brain. The assembly of Aβ peptides into filaments that end at residue 42 is a central event. Yang et al . used electron cryo–electron microscopy to determine the structures of Aβ42 filaments from human brain (see the Perspective by Willem and Fändrich). They identified two types of related S-shaped filaments, each consisting of two identical protofilaments. These structures will inform the development of better in vitro and animal models, inhibitors of Aβ42 assembly, and imaging agents with increased specificity and sensitivity. —SMH