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

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

Assembly of recombinant tau into filaments identical to those of Alzheimer’s disease and chronic traumatic encephalopathy

“…Our work described here and performed previously (Zhang et al, 2019;Shi, Zhang, et al, 2021) illustrates this for tau. Similar observations have been made for amyloid-β (Bertini et al, 2011;Lu et al, 2013;Xiao et al, 2015, p. 201;Wälti et al, 2016;Kollmer et al, 2019;Yang et al, 2022), α-synuclein (Tuttle et al, 2016;B. Li et al, 2018;Y.…”

The 3D structure of lipidic fibrils of α-synuclein

“…S12-S18). The conversion of the SUVs used for the preparation of the lipidic fibrils to such small lipid aggregates upon fibril formation was confirmed by 31 P ssNMR (Fig. S19).…”

High-throughput cryo-EM structure determination of amyloids

“…Similar observations have also been made for other proteins. Filaments of amyloid- 17,18 -synuclein 19 , serum amyloid A 20,21 protein, TAR DNA-binding protein 43 (TDP-43) 22 and the prion protein 23,24 that were extracted from diseased tissue were different from those assembled in vitro.…”