| First Author | Ruiz-Riquelme A | Year | 2021 |
| Journal | Acta Neuropathol Commun | Volume | 9 |
| Issue | 1 | Pages | 83 |
| PubMed ID | 33971978 | Mgi Jnum | J:311724 |
| Mgi Id | MGI:6771447 | Doi | 10.1186/s40478-021-01187-6 |
| Citation | Ruiz-Riquelme A, et al. (2021) Abeta43 aggregates exhibit enhanced prion-like seeding activity in mice. Acta Neuropathol Commun 9(1):83 |
| abstractText | When injected into genetically modified mice, aggregates of the amyloid-beta (Abeta) peptide from the brains of Alzheimer's disease (AD) patients or transgenic AD mouse models seed cerebral Abeta deposition in a prion-like fashion. Within the brain, Abeta exists as a pool of distinct C-terminal variants with lengths ranging from 37 to 43 amino acids, yet the relative contribution of individual C-terminal Abeta variants to the seeding behavior of Abeta aggregates remains unknown. Here, we have investigated the relative seeding activities of Abeta aggregates composed exclusively of recombinant Abeta38, Abeta40, Abeta42, or Abeta43. Cerebral Abeta42 levels were not increased in App(NL-F) knock-in mice injected with Abeta38 or Abeta40 aggregates and were only increased in a subset of mice injected with Abeta42 aggregates. In contrast, significant accumulation of Abeta42 was observed in the brains of all mice inoculated with Abeta43 aggregates, and the extent of Abeta42 induction was comparable to that in mice injected with brain-derived Abeta seeds. Mice inoculated with Abeta43 aggregates exhibited a distinct pattern of cerebral Abeta pathology compared to mice injected with brain-derived Abeta aggregates, suggesting that recombinant Abeta43 may polymerize into a unique strain. Our results indicate that aggregates containing longer Abeta C-terminal variants are more potent inducers of cerebral Abeta deposition and highlight the potential role of Abeta43 seeds as a crucial factor in the initial stages of Abeta pathology in AD. |
