Milligram-scale assembly and NMR fingerprint of tau fibrils adopting the Alzheimer's disease fold.

ABSTRACT: In the Alzheimer's disease (AD) brain, the microtubule-associated protein tau aggregates into paired helical filaments in which each protofilament has a C-shaped conformation. In vitro assembly of tau fibrils adopting this fold is highly valuable for both fundamental and applied studies of AD without requiring patient-brain extracted fibrils. To date, reported methods for forming AD-fold tau fibrils have been irreproducible and sensitive to subtle variations in fibrillization conditions. Here, we describe a route to reproducibly assemble tau fibrils adopting the AD fold on the multi-milligram scale. We investigated the fibrillization conditions of two constructs and found that a tau (297-407) construct that contains four AD phospho-mimetic glutamate mutations robustly formed the C-shaped c

SUBMITTER: Duan P 

PROVIDER: S-EPMC11145547 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature