Microglia-derived ASC specks cross-seed amyloid-β in Alzheimer's disease Venegas Maldonado, Carmen Jesica Kumar, Sathish Franklin, Bernardo S. Dierkes, Tobias Brinkschulte, Rebecca Tejera, Dario Vieira-Saecker, Ana Schwartz, Stephanie Santarelli, Francesco Kummer, Markus P. Griep, Angelika Gelpi, Ellen Beilharz, Michael Riedel, Dietmar Golenbock, Douglas T. Geyer, Matthias Walter, Jochen Latz, Eicke Heneka, Michael T. This work was funded by the Deutsche Forschungsgemeinschaft through the Cluster of Excellence “Immunosensation” (to M.T.H., E.L., M.G. and B.S.F.), the Clinical Research Group (KFO177; to M.T.H., E.L. and J.W.), the SFB670 (E.L.), grant WA1477/6 (J.W.), ERC InflammAct (E.L.), ERC PLAT-IL-1 (B.S.F.), the ERA-NET consortium TracInflam (M.T.H.) and JPND consortium InCure (M.T.H.). 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. 2026-02-24T07:54:06Z 2026-02-24T07:54:06Z 2017-12-20 journal article Venegas, Carmen et al. Microglia-derived ASC specks cross-seed amyloid-β in Alzheimer's disease. Nature 20 December 2017. DOI: 10.1038/nature25158 https://hdl.handle.net/10481/111414 10.1038/nature25158 eng http://creativecommons.org/licenses/by-nc-nd/3.0/ open access Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License Springer Nature