| First Author | Zielinski M | Year | 2023 |
| Journal | Nat Neurosci | Volume | 26 |
| Issue | 12 | Pages | 2073-2080 |
| PubMed ID | 37973869 | Mgi Jnum | J:348885 |
| Mgi Id | MGI:7645583 | Doi | 10.1038/s41593-023-01484-4 |
| Citation | Zielinski M, et al. (2023) Cryo-EM of Abeta fibrils from mouse models find tg-APP(ArcSwe) fibrils resemble those found in patients with sporadic Alzheimer's disease. Nat Neurosci 26(12):2073-2080 |
| abstractText | The use of transgenic mice displaying amyloid-beta (Abeta) brain pathology has been essential for the preclinical assessment of new treatment strategies for Alzheimer's disease. However, the properties of Abeta in such mice have not been systematically compared to Abeta in the brains of patients with Alzheimer's disease. Here, we determined the structures of nine ex vivo Abeta fibrils from six different mouse models by cryogenic-electron microscopy. We found novel Abeta 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(Swe) and APP23 models. The tg-APP(ArcSwe) mice showed an Abeta fibril whose structure resembles the human type I filament found in patients with sporadic Alzheimer's disease. A detailed assessment of the Abeta 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. |
