@misc{10481/111414,
year = {2017},
month = {12},
url = {https://hdl.handle.net/10481/111414},
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.},
organization = {Deutsche Forschungsgemeinschaft},
organization = {Clinical Research Group KFO177, SFB670, WA1477/6, ERC InflammAct, ERC PLAT-IL-1},
organization = {ERA-NET consortium TracInflam},
organization = {JPND consortium InCure},
publisher = {Springer Nature},
title = {Microglia-derived ASC specks cross-seed amyloid-β in Alzheimer's disease},
doi = {10.1038/nature25158},
author = {Venegas Maldonado, Carmen Jesica and Kumar, Sathish and Franklin, Bernardo S. and Dierkes, Tobias and Brinkschulte, Rebecca and Tejera, Dario and Vieira-Saecker, Ana and Schwartz, Stephanie and Santarelli, Francesco and Kummer, Markus P. and Griep, Angelika and Gelpi, Ellen and Beilharz, Michael and Riedel, Dietmar and Golenbock, Douglas T. and Geyer, Matthias and Walter, Jochen and Latz, Eicke and Heneka, Michael T.},
}