8OL2

Murine type II Abeta fibril from APP23 mouse

8OL2 の概要

• エントリーDOI: 10.2210/pdb8ol2/pdb
• EMDBエントリー: 16942
• 分子名称: Amyloid-beta protein 42 (1 entity in total)
• 機能のキーワード: amyloid fibril, protein fibril
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 45200.87

構造登録者

Zielinski, M.,Peralta Reyes, F.S.,Gremer, L.,Schemmert, S.,Frieg, B.,Willuweit, A.,Donner, L.,Elvers, M.,Nilsson, L.N.G.,Syvanen, S.,Sehlin, D.,Ingelsson, M.,Willbold, D.,Schroeder, G.F. (登録日: 2023-03-30, 公開日: 2023-11-29, 最終更新日: 2023-12-13)

主引用文献

Zielinski, M.,Peralta Reyes, F.S.,Gremer, L.,Schemmert, S.,Frieg, B.,Schafer, L.U.,Willuweit, A.,Donner, L.,Elvers, M.,Nilsson, L.N.G.,Syvanen, S.,Sehlin, D.,Ingelsson, M.,Willbold, D.,Schroder, G.F.
Cryo-EM of A beta fibrils from mouse models find tg-APP ArcSwe fibrils resemble those found in patients with sporadic Alzheimer's disease.
Nat.Neurosci., 26:2073-2080, 2023

PubMed Abstract: The use of transgenic mice displaying amyloid-β (Aβ) brain pathology has been essential for the preclinical assessment of new treatment strategies for Alzheimer's disease. However, the properties of Aβ in such mice have not been systematically compared to Aβ in the brains of patients with Alzheimer's disease. Here, we determined the structures of nine ex vivo Aβ fibrils from six different mouse models by cryogenic-electron microscopy. We found novel Aβ fibril structures in the APP/PS1, ARTE10 and tg-SwDI models, whereas the human type II filament fold was found in the ARTE10, tg-APP and APP23 models. The tg-APP mice showed an Aβ fibril whose structure resembles the human type I filament found in patients with sporadic Alzheimer's disease. A detailed assessment of the Aβ fibril structure is key to the selection of adequate mouse models for the preclinical development of novel plaque-targeting therapeutics and positron emission tomography imaging tracers in Alzheimer's disease.

PubMed: 37973869
DOI: 10.1038/s41593-023-01484-4

実験手法

ELECTRON MICROSCOPY (3 Å)