| Literature DB >> 29293211 |
Carmen Venegas1, Sathish Kumar2, Bernardo S Franklin3, Tobias Dierkes1,3, Rebecca Brinkschulte3, Dario Tejera1, Ana Vieira-Saecker1, Stephanie Schwartz1, Francesco Santarelli1, Markus P Kummer1, Angelika Griep1, Ellen Gelpi4, Michael Beilharz3, Dietmar Riedel5, Douglas T Golenbock6, Matthias Geyer3, Jochen Walter2, Eicke Latz3,6,7, Michael T Heneka1,6,7.
Abstract
The spreading of pathology within and between brain areas is a hallmark of neurodegenerative disorders. In patients with Alzheimer's disease, deposition of amyloid-β 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-β and increase the formation of amyloid-β oligomers and aggregates, acting as an inflammation-driven cross-seed for amyloid-β pathology. Here we show that intrahippocampal injection of ASC specks resulted in spreading of amyloid-β pathology in transgenic double-mutant APPSwePSEN1dE9 mice. By contrast, homogenates from brains of APPSwePSEN1dE9 mice failed to induce seeding and spreading of amyloid-β pathology in ASC-deficient APPSwePSEN1dE9 mice. Moreover, co-application of an anti-ASC antibody blocked the increase in amyloid-β pathology in APPSwePSEN1dE9 mice. These findings support the concept that inflammasome activation is connected to seeding and spreading of amyloid-β pathology in patients with Alzheimer's disease.Entities:
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Year: 2017 PMID： 29293211 DOI： 10.1038/nature25158
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962