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bioRxiv · 10.1101/2020.03.06.981381

Molecular structure of a prevalent amyloid-β fibril polymorph from Alzheimer's disease brain tissue

Ghosh, U.·Thurber, K. R.·Yau, W.-M.·Tycko, R.
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Abstract

Amyloid-{beta} (A{beta}) fibrils exhibit self-propagating, molecular-level polymorphisms that may underlie variations in clinical and pathological characteristics of Alzheimers disease. We report the molecular structure of a specific brain-derived polymorph that has been identified as the most prevalent polymorph of 40-residue A{beta} fibrils in cortical tissue of Alzheimers disease patients. This structure, developed from cryo-electron microscopy and supported by solid state NMR data, differs qualitatively from all previously described A{beta} fibril structures, both in its molecular conformation and its organization of cross-{beta} subunits. Knowledge of this brain-derived fibril structure may contribute to the development of structure-specific amyloid imaging agents and aggregation inhibitors with greater diagnostic and therapeutic utility.

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Ghosh, U., Thurber, K. R., Yau, W.-M., Tycko, R.. 2020-03-07. Molecular structure of a prevalent amyloid-β fibril polymorph from Alzheimer's disease brain tissue. https://doi.org/10.1101/2020.03.06.981381

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