| First Author | Venegas C | Year | 2017 |
| Journal | Nature | Volume | 552 |
| Issue | 7685 | Pages | 355-361 |
| PubMed ID | 29293211 | Mgi Jnum | J:334848 |
| Mgi Id | MGI:6757515 | Doi | 10.1038/nature25158 |
| Citation | Venegas C, et al. (2017) Microglia-derived ASC specks cross-seed amyloid-beta in Alzheimer's disease. Nature 552(7685):355-361 |
| abstractText | The spreading of pathology within and between brain areas is a hallmark of neurodegenerative disorders. In patients with Alzheimer's disease, deposition of amyloid-beta is accompanied by activation of the innate immune system and involves inflammasome-dependent formation of ASC specks in microglia. ASC specks released by microglia bind rapidly to amyloid-beta and increase the formation of amyloid-beta oligomers and aggregates, acting as an inflammation-driven cross-seed for amyloid-beta pathology. Here we show that intrahippocampal injection of ASC specks resulted in spreading of amyloid-beta pathology in transgenic double-mutant APPSwePSEN1dE9 mice. By contrast, homogenates from brains of APPSwePSEN1dE9 mice failed to induce seeding and spreading of amyloid-beta pathology in ASC-deficient APPSwePSEN1dE9 mice. Moreover, co-application of an anti-ASC antibody blocked the increase in amyloid-beta pathology in APPSwePSEN1dE9 mice. These findings support the concept that inflammasome activation is connected to seeding and spreading of amyloid-beta pathology in patients with Alzheimer's disease. |
