Research output per year
Research output per year
Changjun Yin*, Susanne Ackermann, Zhe Ma, Sarajo K. Mohanta, Chuankai Zhang, Yuanfang Li, Sandor Nietzsche, Martin Westermann, Li Peng, Desheng Hu, Sai Vineela Bontha, Prasad Srikakulapu, Michael Beer, Remco T. A. Megens, Sabine Steffens, Markus Hildner, Luke D. Halder, Hans-Henning Eckstein, Jaroslav Pelisek, Jochen Herms
Research output: Contribution to journal › Article › Academic › peer-review
Apolipoprotein-E (ApoE) has been implicated in Alzheimer's disease, atherosclerosis, and other unresolvable inflammatory conditions but a common mechanism of action remains elusive. We found in ApoE-deficient mice that oxidized lipids activated the classical complement cascade (CCC), resulting in leukocyte infiltration of the choroid plexus (ChP). All human ApoE iso-forms attenuated CCC activity via high-affinity binding to the activated CCC-initiating C1q protein (K-D similar to 140-580 pM) in vitro, and C1q-ApoE complexes emerged as markers for ongoing complement activity of diseased ChPs, A beta plaques, and atherosclerosis in vivo. C1q-ApoE complexes in human ChPs, A beta plaques, and arteries correlated with cognitive decline and atherosclerosis, respectively. Treatment with small interfering RNA (siRNA) against C5, which is formed by all complement pathways, attenuated murine ChP inflammation, A beta-associated microglia accumulation, and atherosclerosis. Thus, ApoE is a direct checkpoint inhibitor of unresolvable inflammation, and reducing C5 attenuates disease burden.
Original language | English |
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Pages (from-to) | 496-506 |
Number of pages | 23 |
Journal | Nature Medicine |
Volume | 25 |
Issue number | 3 |
DOIs | |
Publication status | Published - Mar 2019 |
Research output: Contribution to journal › Erratum / corrigendum / retractions › Academic