Journal: J Mol Biol / Year: 2024 Title: Cryo-EM Analysis of the Effect of Seeding with Brain-derived Aβ Amyloid Fibrils. Authors: Peter Benedikt Pfeiffer / Marijana Ugrina / Nadine Schwierz / Christina J Sigurdson / Matthias Schmidt / Marcus Fändrich / Abstract: Aβ amyloid fibrils from Alzheimer's brain tissue are polymorphic and structurally different from typical in vitro formed Aβ fibrils. Here, we show that brain-derived (ex vivo) fibril structures can ...Aβ amyloid fibrils from Alzheimer's brain tissue are polymorphic and structurally different from typical in vitro formed Aβ fibrils. Here, we show that brain-derived (ex vivo) fibril structures can be proliferated by seeding in vitro. The proliferation reaction is only efficient for one of the three abundant ex vivo Aβ fibril morphologies, which consists of two peptide stacks, while the inefficiently proliferated fibril morphologies contain four or six peptide stacks. In addition to the seeded fibril structures, we find that de novo nucleated fibril structures can emerge in seeded samples if the seeding reaction is continued over multiple generations. These data imply a competition between de novo nucleation and seed extension and suggest further that seeding favours the outgrowth of fibril morphologies that contain fewer peptide stacks.
Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Detector mode: COUNTING / Number grids imaged: 1 / Number real images: 3018 / Average exposure time: 10.0 sec. / Average electron dose: 53.79 e/Å2
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
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