| First Author | Purro SA | Year | 2023 |
| Journal | PLoS One | Volume | 18 |
| Issue | 11 | Pages | e0294465 |
| PubMed ID | 37976283 | Mgi Jnum | J:346798 |
| Mgi Id | MGI:7550053 | Doi | 10.1371/journal.pone.0294465 |
| Citation | Purro SA, et al. (2023) Two mouse models of Alzheimer's disease accumulate amyloid at different rates and have distinct Abeta oligomer profiles unaltered by ablation of cellular prion protein. PLoS One 18(11):e0294465 |
| abstractText | Oligomers formed from monomers of the amyloid beta-protein (Abeta) are thought to be central to the pathogenesis of Alzheimer's disease (AD). Unsurprisingly for a complex disease, current mouse models of AD fail to fully mimic the clinical disease in humans. Moreover, results obtained in a given mouse model are not always reproduced in a different model. Cellular prion protein (PrPC) is now an established receptor for Abeta oligomers. However, studies of the Abeta-PrPC interaction in different mouse models have yielded contradictory results. Here we performed a longitudinal study assessing a range of biochemical and histological features in the commonly used J20 and APP-PS1 mouse models. Our analysis demonstrated that PrPC ablation had no effect on amyloid accumulation or oligomer production. However, we found that APP-PS1 mice had higher levels of oligomers, that these could bind to recombinant PrPC, and were recognised by the OC antibody which distinguishes parallel, in register fibrils. On the other hand, J20 mice had a lower level of Abeta oligomers, which did not interact with PrPC when tested in vitro and were OC-negative. These results suggest the two mouse models produce diverse Abeta assemblies that could interact with different targets, highlighting the necessity to characterise the conformation of the Abeta oligomers concomitantly with the toxic cascade elicited by them. Our results provide an explanation for the apparent contradictory results found in APP-PS1 mice and the J20 mouse line in regards to Abeta toxicity mediated by PrPC. |
