8OL6

Murine type II Abeta fibril from tgAPPSwe mouse

Summary for 8OL6

• Entry DOI: 10.2210/pdb8ol6/pdb
• EMDB information: 16952
• Descriptor: Amyloid-beta protein 42 (1 entity in total)
• Functional Keywords: amyloid fibril, protein fibril
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 10
• Total formula weight: 45200.87

Authors

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. (deposition date: 2023-03-30, release date: 2023-11-29, Last modification date: 2023-12-13)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.8 Å)