articleNatureNov 29, 2023HYBRID OA

Disease-specific tau filaments assemble via polymorphic intermediates

MRC Laboratory of Molecular Biology · Thermo Fisher Scientific (Netherlands)

PubMed
Indexed incrossrefpubmed

Abstract

Abstract Intermediate species in the assembly of amyloid filaments are believed to play a central role in neurodegenerative diseases and may constitute important targets for therapeutic intervention 1,2 . However, structural information about intermediate species has been scarce and the molecular mechanisms by which amyloids assemble remain largely unknown. Here we use time-resolved cryogenic electron microscopy to study the in vitro assembly of recombinant truncated tau (amino acid residues 297–391) into paired helical filaments of Alzheimer’s disease or into filaments of chronic traumatic encephalopathy 3 . We report the formation of a shared first intermediate amyloid filament, with an ordered core…

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