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DOI	10.1073/pnas.2023089118
	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.
发表日期	2021
ISSN	00278424
卷号	118 期号:4
英文摘要	Amyloid-β (Aβ) fibrils exhibit self-propagating, molecular-level polymorphisms that may contribute to variations in clinical and pathological characteristics of Alzheimer’s disease (AD). We report the molecular structure of a specific fibril polymorph, formed by 40-residue Aβ peptides (Aβ40), that is derived from cortical tissue of an AD patient by seeded fibril growth. The structure is determined from cryogenic electron microscopy (cryoEM) images, supplemented by mass-per-length (MPL) measurements and solid-state NMR (ssNMR) data. Previous ssNMR studies with multiple AD patients had identified this polymorph as the most prevalent brain-derived Aβ40 fibril polymorph from typical AD patients. The structure, which has 2.8-Å resolution according to standard criteria, differs qualitatively from all previously described Aβ fibril structures, both in its molecular conformations and its organization of cross-β subunits. Unique features include twofold screw symmetry about the fibril growth axis, despite an MPL value that indicates three Aβ40 molecules per 4.8-Å β-sheet spacing, a four-layered architecture, and fully extended conformations for molecules in the central two cross-β layers. The cryoEM density, ssNMR data, and MPL data are consistent with β-hairpin conformations for molecules in the outer cross-β layers. 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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Alzheimer’s disease; Amyloid structure; Cryo-electron microscopy; Solid-state NMR
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180925
作者单位	Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, United States
推荐引用方式 GB/T 7714	Ghosh U.,Thurber K.R.,Yau W.-M.,等. Molecular structure of a prevalent amyloid-β fibril polymorph from Alzheimer’s disease brain tissue[J],2021,118(4).
APA	Ghosh U.,Thurber K.R.,Yau W.-M.,&Tycko R..(2021).Molecular structure of a prevalent amyloid-β fibril polymorph from Alzheimer’s disease brain tissue.Proceedings of the National Academy of Sciences of the United States of America,118(4).
MLA	Ghosh U.,et al."Molecular structure of a prevalent amyloid-β fibril polymorph from Alzheimer’s disease brain tissue".Proceedings of the National Academy of Sciences of the United States of America 118.4(2021).