ApoE attenuates unresolvable inflammation by complex formation with activated C1q
Open accessAbstract
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 isoforms attenuated CCC activity via high-affinity binding to the activated CCC-initiating C1q protein (K D~140-580 pM) in vitro, and C1q-ApoE complexes emerged as markers for ongoing complement activity of diseased ChPs, Aβ plaques, and atherosclerosis in vivo. C1q-ApoE complexes in human ChPs, Aβ 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, Aβ-associated microglia accumulation, and atherosclerosis. Thus, ApoE is a direct checkpoint inhibitor of unresolvable inflammation, and reducing C5 attenuates disease burden.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
BBB breakdown in AD could be related to altered endothelial junctions.
“It has been reported that BBB breakdown in AD could be related to altered endothelial junctions,[ 22 ]”
From Multifunctional Nanostructure RAP‐RL Rescues Alzheimer's Cognitive Deficits through Remodeling the Neurovascular Unit (2021) · cites this paper as [22]
The Results section (‘ChP lipid deposits, inflammation, and interferon signatures’; page unavailable) reports BBB breakdown in ApoE-deficient and ApoE4 mouse models, using perivascular immunoglobulin as a marker. It does not link BBB breakdown in people with AD to altered endothelial junctions; the junctional explanation is unsupported by our copy. (LLM, conf=0.83)
Experimental — accuracy not yet measuredPerivascular Aβ impairs cerebral vessel structure and CBF.
“Perivascular Aβ impairs the cerebral vessels structure and CBF.[ 22 , 29 ]”
From Multifunctional Nanostructure RAP‐RL Rescues Alzheimer's Cognitive Deficits through Remodeling the Neurovascular Unit (2021) · cites this paper as [22]
The Results section on Aβ plaques describes Aβ–ApoE complexes and plaque-associated inflammation, while the BBB assay section describes a measure of barrier integrity; neither links perivascular Aβ to impaired vessel structure. Searches for CBF, cerebral blood flow, and vascular effects of perivascular amyloid found no passage addressing the claimed effect on blood flow. (LLM, conf=0.73)
Experimental — accuracy not yet measuredIn neurodegeneration, the complement pathway is activated, and inhibiting C1q or C3 reduces neuroinflammation, Aβ plaques, and synapse loss.
“In neurodegeneration, the complement pathway is activated, and inhibiting the complement proteins C1q or C3 results in less neuroinflammation, Aβ plaques and synapse loss29,30.”
From Exercise plasma boosts memory and dampens brain inflammation via clusterin (2021) · cites this paper as [29]
The activation of C1Q can be attenuated by APOE.
“Interestingly, the activation of C1Q can be attenuated by another molecule of the PIG network, APOE (Yin et al. , 2019).”
From Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease (2020) · cites this paper as Yin et al., 2019
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Phases of Aβ-deposition in the human brain and its relevance for the development of AD
Thal, D. R., Rüb, U., Orantes, M., & Braak, H. (2002) · Neurology · doi:10.1212/wnl.58.12.1791 · Cited by 3,490 · see citing works
Complement and microglia mediate early synapse loss in Alzheimer mouse models
Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., et al. (2016) · Science · doi:10.1126/science.aad8373 · Cited by 3,343 · see citing works
The Classical Complement Cascade Mediates CNS Synapse Elimination
Stevens, B., Allen, N. J., Vazquez, L. E., Howell, G. R., Christopherson, K. S., Nouri, N., Micheva, K. D., Mehalow, A. K., Huberman, A. D., Stafford, B., et al. (2007) · Cell · doi:10.1016/j.cell.2007.10.036 · Cited by 3,313 · see citing works
Braak, H., Alafuzoff, I., Arzberger, T., Kretzschmar, H., & Del Tredici, K. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0127-z · Cited by 3,172 · see citing works
Self-citationHyman, B. T., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Carrillo, M. C., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., et al. (2012) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.10.007 · Cited by 3,092 · see citing works
Direct observation of individual endogenous protein complexes in situ by proximity ligation
Söderberg, O., Gullberg, M., Jarvius, M., Ridderstråle, K., Leuchowius, K.-J., Jarvius, J., Wester, K., Hydbring, P., Bahram, F., Larsson, L.-G., et al. (2006) · Nature Methods · doi:10.1038/nmeth947 · Cited by 2,419 · see citing works
The immune system in atherosclerosis
Hansson, G. K., & Hermansson, A. (2011) · Nature Immunology · doi:10.1038/ni.2001 · Cited by 2,331 · see citing works
Integrated Systems Approach Identifies Genetic Nodes and Networks in Late-Onset Alzheimer’s Disease
Zhang, B., Gaiteri, C., Bodea, L.-G., Wang, Z., McElwee, J., Podtelezhnikov, A. A., Zhang, C., Xie, T., Tran, L., Dobrin, R., et al. (2013) · Cell · doi:10.1016/j.cell.2013.03.030 · Cited by 1,657 · see citing works
Self-citationAlbert Hofman, D., Ott, A., Breteler, M. M. B., Bots, M. L., Slooter, A. J. C., van Harskamp, F., van Duijn, C. M., Broeckhoven, C. V., & Grobbee, D. E. (1997) · The Lancet · doi:10.1016/s0140-6736(96)09328-2 · Cited by 1,365 · see citing works
Apolipoprotein E controls cerebrovascular integrity via cyclophilin A
Bell, R. D., Winkler, E. A., Singh, I., Sagare, A. P., Deane, R., Wu, Z., Holtzman, D. M., Betsholtz, C., Armulik, A., Sallstrom, J., et al. (2012) · Nature · doi:10.1038/nature11087 · Cited by 1,293 · see citing works
Complement regulators and inhibitory proteins
Zipfel, P. F., & Skerka, C. (2009) · Nature reviews. Immunology · doi:10.1038/nri2620 · Cited by 1,268 · see citing works
Self-citationApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy
Initiative, A. D. N., Shi, Y., Yamada, K., Liddelow, S. A., Smith, S. T., Zhao, L., Luo, W., Tsai, R. M., Spina, S., Grinberg, L. T., et al. (2017) · Nature · doi:10.1038/nature24016 · Cited by 1,220 · see citing works
Origin, fate and dynamics of macrophages at central nervous system interfaces
Goldmann, T., Wieghofer, P., Jordão, M. J. C., Prutek, F., Hagemeyer, N., Frenzel, K., Amann, L., Staszewski, O., Kierdorf, K., Krueger, M., et al. (2016) · Nature Immunology · doi:10.1038/ni.3423 · Cited by 1,209 · see citing works
Anti-inflammatory Agents: Present and Future
Dinarello, C. A. (2010) · Cell · doi:10.1016/j.cell.2010.02.043 · Cited by 1,095 · see citing works
Anti-Inflammatory Therapy in Chronic Disease: Challenges and Opportunities
Tabas, I., & Glass, C. K. (2013) · Science · doi:10.1126/science.1230720 · Cited by 1,093 · see citing works
Aβ42‐driven cerebral amyloidosis in transgenic mice reveals early and robust pathology
Radde, R., Bolmont, T., Kaeser, S. A., Coomaraswamy, J., Lindau, D., Stoltze, L., Calhoun, M. E., Jäggi, F., Wolburg, H., Gengler, S., et al. (2006) · The EMBO Reports · doi:10.1038/sj.embor.7400784 · Cited by 986 · see citing works
The anatomical and cellular basis of immune surveillance in the central nervous system
Ransohoff, R. M., & Engelhardt, B. (2012) · Nature reviews. Immunology · doi:10.1038/nri3265 · Cited by 975 · see citing works
Lack of apolipoprotein E dramatically reduces amyloid β-peptide deposition
Bales, K. R., Verina, T., Dodel, R. C., Du, Y., Altstiel, L., Bender, M., Hyslop, P., Johnstone, E. M., Little, S. P., Cummins, D. J., et al. (1997) · Nature Genetics · doi:10.1038/ng1197-263 · Cited by 830 · see citing works
Apolipoprotein E and Apolipoprotein E Receptors: Normal Biology and Roles in Alzheimer Disease
Holtzman, D. M., Herz, J., & Bu, G. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006312 · Cited by 782 · see citing works
Natural History and Histological Classification of Atherosclerotic Lesions
Stary, H. C. (2000) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.20.5.1177 · Cited by 752 · see citing works
Development and functions of the choroid plexus–cerebrospinal fluid system
Lun, M. P., Monuki, E. S., & Lehtinen, M. K. (2015) · Nature reviews. Neuroscience · doi:10.1038/nrn3921 · Cited by 682 · see citing works
Three-Dimensional Structure of the LDL Receptor-Binding Domain of Human Apolipoprotein E
Wilson, C., Wardell, M. R., Weisgraber, K. H., Mahley, R. W., & Agard, D. A. (1991) · Science · doi:10.1126/science.2063194 · Cited by 678 · see citing works
A complement–microglial axis drives synapse loss during virus-induced memory impairment
Vasek, M. J., Garber, C., Dorsey, D., Durrant, D. M., Bollman, B., Soung, A., Yu, J., Perez-Torres, C., Frouin, A., Wilton, D. K., et al. (2016) · Nature · doi:10.1038/nature18283 · Cited by 671 · see citing works
Aging-induced type I interferon response at the choroid plexus negatively affects brain function
Baruch, K., Deczkowska, A., David, E., Castellano, J. M., Miller, O., Kertser, A., Berkutzki, T., Barnett-Itzhaki, Z., Bezalel, D., Wyss-Coray, T., et al. (2014) · Science · doi:10.1126/science.1252945 · Cited by 615 · see citing works
ApoE and Aβ in Alzheimer’s Disease: Accidental Encounters or Partners?
Kanekiyo, T., Xu, H., & Bu, G. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.045 · Cited by 608 · see citing works
Apolipoprotein E: structure determines function, from atherosclerosis to Alzheimer's disease to AIDS
Mahley, R. W., Weisgraber, K. H., & Huang, Y. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r800069-jlr200 · Cited by 580 · see citing works
Complement factor H binds malondialdehyde epitopes and protects from oxidative stress
Weismann, D., Hartvigsen, K., Lauer, N., Bennett, K. L., Scholl, H. P. N., Issa, P. C., Cano, M., Brandstätter, H., Tsimikas, S., Skerka, C., et al. (2011) · Nature · doi:10.1038/nature10449 · Cited by 533 · see citing works
Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice
Que, X., Hung, M.-Y., Yeang, C., Gonen, A., Prohaska, T. A., Sun, X., Diehl, C., Määttä, A., Gaddis, D. E., Bowden, K., et al. (2018) · Nature · doi:10.1038/s41586-018-0198-8 · Cited by 529 · see citing works
Self-citationApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcription and Aβ Secretion
Huang, Y.-W. A., Zhou, B., Wernig, M., & Südhof, T. C. (2017) · Cell · doi:10.1016/j.cell.2016.12.044 · Cited by 528 · see citing works
Novel mechanisms and functions of complement
Hajishengallis, G., Reis, E. S., Mastellos, D. C., Ricklin, D., & Lambris, J. D. (2017) · Nature Immunology · doi:10.1038/ni.3858 · Cited by 484 · see citing works
Complement in Immune and Inflammatory Disorders: Pathophysiological Mechanisms
Ricklin, D., & Lambris, J. D. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1203487 · Cited by 480 · see citing works
Prevention of atherosclerosis in apolipoprotein E-deficient mice by bone marrow transplantation
Linton, M. F., Atkinson, J. B., & Fazio, S. (1995) · Science · doi:10.1126/science.7863332 · Cited by 478 · see citing works
Strittmatter, W. J., Saunders, A. M., Goedert, M., Weisgraber, K. H., Dong, L. M., Jakes, R., Huang, D. Y., Pericak-Vance, M., Schmechel, D., & Roses, A. D. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.23.11183 · Cited by 474 · see citing works
Alafuzoff, I., Arzberger, T., Al‐Sarraj, S., Bodi, I., Bogdanovic, N., Braak, H., Bugiani, O., Del‐Tredici, K., Ferrer, I., Gelpi, E., et al. (2008) · Brain Pathology · doi:10.1111/j.1750-3639.2008.00147.x · Cited by 467 · see citing works
Self-citationApoE4 Accelerates Early Seeding of Amyloid Pathology
Liu, C.-C., Zhao, N., Fu, Y., Wang, N., Linares, C., Tsai, C.-W., & Bu, G. (2017) · Neuron · doi:10.1016/j.neuron.2017.11.013 · Cited by 451 · see citing works
Wang, C., Najm, R., Xu, Q., Jeong, D.-E., Walker, D., Balestra, M. E., Yoon, S. Y., Yuan, H., Li, G., Miller, Z. A., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0004-z · Cited by 428 · see citing works
Apolipoprotein e sets the stage: response to injury triggers neuropathology
Mahley, R. W., & Huang, Y. (2012) · Neuron · doi:10.1016/j.neuron.2012.11.020 · Cited by 412 · see citing works
Innate sensing of oxidation-specific epitopes in health and disease
Binder, C. J., Papac-Milicevic, N., & Witztum, J. L. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.63 · Cited by 403 · see citing works
Self-citationA major role for cardiovascular burden in age-related cognitive decline
Qiu, C., & Fratiglioni, L. (2015) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2014.223 · Cited by 401 · see citing works
Gräbner, R., Lötzer, K., Döpping, S., Hildner, M., Radke, D., Beer, M., Spanbroek, R., Lippert, B., Reardon, C. A., Getz, G. S., et al. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20080752 · Cited by 395 · see citing works
Self-citationThe 5-lipoxygenase pathway promotes pathogenesis of hyperlipidemia-dependent aortic aneurysm
Zhao, L., Moos, M. P. W., Gräbner, R., Pédrono, F., Fan, J., Kaiser, B., John, N. F. S., Schmidt, S., Spanbroek, R., Lötzer, K., et al. (2004) · Nature Medicine · doi:10.1038/nm1099 · Cited by 353 · see citing works
Self-citationComplement — tapping into new sites and effector systems
Kolev, M. V., Friec, G. L., & Kemper, C. (2014) · Nature reviews. Immunology · doi:10.1038/nri3761 · Cited by 350 · see citing works
Schwartz, M., & Baruch, K. (2014) · The EMBO Journal · doi:10.1002/embj.201386609 · Cited by 349 · see citing works
Absence of C1q Leads to Less Neuropathology in Transgenic Mouse Models of Alzheimer's Disease
Fonseca, M. I., Zhou, J., Botto, M., & Tenner, A. J. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.0901-04.2004 · Cited by 345 · see citing works
Apo E structure determines VLDL clearance and atherosclerosis risk in mice
Knouff, C., Hinsdale, M. E., Mezdour, H., Altenburg, M. K., Watanabe, M., Quarfordt, S. H., Sullivan, P. M., & Maeda, N. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6172 · Cited by 324 · see citing works
ApoE facilitates the microglial response to amyloid plaque pathology
Ulrich, J. D., Ulland, T. K., Mahan, T. E., Nyström, S., Nilsson, K. P., Song, W. M., Zhou, Y., Reinartz, M., Choi, S., Jiang, H., et al. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20171265 · Cited by 297 · see citing works
Macedo, A. C. L., & Isaac, L. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00055 · Cited by 293 · see citing works
Systematic Review of Guidelines for the Management of Asymptomatic and Symptomatic Carotid Stenosis
Abbott, A. L., Paraskevas, K. I., Kakkos, S. K., Golledge, J., Eckstein, H., Díaz‐Sandoval, L. J., Cao, L., Fu, Q., Wijeratne, T., Leung, T. W. H., et al. (2015) · Stroke · doi:10.1161/strokeaha.115.003390 · Cited by 283 · see citing works
Self-citationCerebrovascular Effects of Apolipoprotein E: Implications for Alzheimer Disease
Zlokovic, B. V. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.2152 · Cited by 263 · see citing works
Hu, D., Mohanta, S. K., Yin, C., Peng, L., Ma, Z., Srikakulapu, P., Grassia, G., MacRitchie, N. A., Dever, G., Gordon, P., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.05.015 · Cited by 224 · see citing works
Self-citationAge-Dependent Effects of apoE Reduction Using Antisense Oligonucleotides in a Model of β-amyloidosis
Huynh, T.-P. V., Liao, F., Francis, C. M., Robinson, G. O., Serrano, J. R., Jiang, H., Roh, J., Finn, M. B., Sullivan, P. M., Esparza, T. J., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.11.014 · Cited by 209 · see citing works
Assessment of β-amyloid deposits in human brain: a study of the BrainNet Europe Consortium
Alafuzoff, I., Thal, D. R., Arzberger, T., Bogdanovic, N., Al-Sarraj, S., Bodi, I., Boluda, S., Bugiani, O., Duyckaerts, C., Gelpi, E., et al. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0485-4 · Cited by 193 · see citing works
Self-citationReporting standards for carotid interventions from the Society for Vascular Surgery
Timaran, C. H., McKinsey, J. F., Schneider, P. A., & Littooy, F. N. (2011) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2010.11.122 · Cited by 132 · see citing works
New tricks for an ancient system: Physiological and pathological roles of complement in the CNS
Tenner, A. J., Stevens, B., & Woodruff, T. M. (2018) · Molecular Immunology · doi:10.1016/j.molimm.2018.06.264 · Cited by 112 · see citing works
Girija, U. V., Gingras, A. R., Marshall, J. E., Panchal, R., Sheikh, M. A., Harper, J. A., Gál, P., Schwaeble, W., Mitchell, D. A., Moody, P. C. E., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1311113110 · Cited by 109 · see citing works
Wendorff, C., Wendorff, H., Pelisek, J., et al. (2015) · Stroke · doi:10.1161/strokeaha.115.010558 · Cited by 94 · see citing works
Self-citationAlternation of histone and DNA methylation in human atherosclerotic carotid plaques
Napieralski, R., Wagner, E., Gebhard, H., Schmitt, M., Zimmermann, A., Eckstein, H.-H., Greißel, A., Culmes, M., Zernecke, A., & Pelisek, J. (2015) · Thrombosis and Haemostasis · doi:10.1160/th14-10-0852 · Cited by 83 · see citing works
Self-citationStaphylococcus aureus Proteins Sbi and Efb Recruit Human Plasmin to Degrade Complement C3 and C3b
Koch, T. K., Reuter, M., Barthel, D., Böhm, S., van den Elsen, J. M. H., Kraiczy, P., Zipfel, P. F., & Skerka, C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0047638 · Cited by 71 · see citing works
Self-citationHaege, S., Einer, C., Thiele, S., Mueller, W., Nietzsche, S., Lupp, A., Mackay, F., Schulz, S., & Stumm, R. K. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042814 · Cited by 49 · see citing works
Self-citationHaapasalo, K., van Kessel, K. P. M., Nissilä, E., Metso, J., Johansson, T., Miettinen, S., Varjosalo, M. T., Kirveskari, J., Kuusela, P., Chroni, A., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.669226 · Cited by 43 · see citing works
Moore, G. R. W., Laule, C., Leung, E., Pavlova, V., Morgan, B. P., & Esiri, M. M. (2016) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlw017 · Cited by 27 · see citing works
Laser-Capture Microdissection of Hyperlipidemic/ApoE−/− Mouse Aorta Atherosclerosis
Beer, M., Doepping, S., Hildner, M., et al. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-163-5_35 · Cited by 21 · see citing works
Self-citationYin, C., Mohanta, S. K., Ma, Z., et al. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-2929-0_20 · Cited by 12 · see citing works
Self-citationArlaud, G. J., Bı́ró, A., & Ling, W. L. (2011) · Journal of Lipids · doi:10.1155/2011/376092 · Cited by 11 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [60]Franklin K George P The Mouse Brain in Stereotaxic Coordinates, Compact 3rd Edition 2007
Cited by
Sorted by citations
Borén, J., Chapman, M. J., Krauss, R. M., Packard, C. J., Bentzon, J. F., Binder, C. J., Daemen, M. J., Demer, L. L., Hegele, R. A., Nicholls, S. J., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz962 · Cited by 1,601 · see citing works
Self-citationSpatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease
Chen, W.-T., Lu, A., Craessaerts, K., Pavie, B., Sala Frigerio, C., Corthout, N., Qian, X., Laláková, J., Kühnemund, M., Voytyuk, I., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.038 · Cited by 949 · see citing works
Exercise plasma boosts memory and dampens brain inflammation via clusterin
De Miguel, Z., Khoury, N., Betley, M. J., Lehallier, B., Willoughby, D., Olsson, N., Yang, A. C., Hahn, O., Lu, N., Vest, R. T., et al. (2021) · Nature · doi:10.1038/s41586-021-04183-x · Cited by 422 · see citing works
Microglia modulate neurodegeneration in Alzheimer’s and Parkinson’s diseases
Bartels, T., De Schepper, S., & Hong, S. (2020) · Science · doi:10.1126/science.abb8587 · Cited by 412 · see citing works
TLR4 Cross-Talk With NLRP3 Inflammasome and Complement Signaling Pathways in Alzheimer's Disease
Yang, J., Wise, L., & Fukuchi, K.-I. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00724 · Cited by 387 · see citing works
Immune Signaling in Neurodegeneration
Hammond, T. R., Marsh, S. E., & Stevens, B. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.016 · Cited by 336 · see citing works
Emerging roles of innate and adaptive immunity in Alzheimer’s disease
Chen, X., & Holtzman, D. M. (2022) · Immunity · doi:10.1016/j.immuni.2022.10.016 · Cited by 297 · see citing works
Microglia in Brain Development, Homeostasis, and Neurodegeneration
Bohlen, C. J., Friedman, B. A., Dejanovic, B., & Sheng, M. (2019) · Annual Review of Genetics · doi:10.1146/annurev-genet-112618-043515 · Cited by 212 · see citing works
Intersection of pathological tau and microglia at the synapse
Vogels, T., Murgoci, A.-N., & Hromádka, T. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0754-y · Cited by 197 · see citing works
Lee, S., Devanney, N. A., Golden, L. R., Smith, C. T., Schwartz, J. L., Walsh, A. E., Clarke, H. A., Goulding, D. S., Allenger, E. J., Morillo-Segovia, G., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112196 · Cited by 203 · see citing works
Immunotherapy for cardiovascular disease
Lutgens, E., Atzler, D., Döring, Y., Duchene, J., Steffens, S., & Weber, C. (2019) · European Heart Journal · doi:10.1093/eurheartj/ehz283 · Cited by 192 · see citing works
Self-citationHe, L., Davila-Velderrain, J., Sumida, T. S., Hafler, D. A., Kellis, M., & Kulminski, A. M. (2021) · Communications Biology · doi:10.1038/s42003-021-02146-6 · Cited by 181 · see citing works
Zhong, L., Sheng, X., Wang, W., Li, Y., Zhuo, R., Wang, K., Zhang, L., Hu, D.-D., Hong, Y., Chen, L., et al. (2023) · Immunity · doi:10.1016/j.immuni.2023.06.016 · Cited by 168 · see citing works
Self-citationZhou, J., Wade, S. D., Graykowski, D., Xiao, M.-F., Zhao, B., Giannini, L. A. A., Hanson, J. E., van Swieten, J. C., Sheng, M., Worley, P. F., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.adf0141 · Cited by 152 · see citing works
Microglial phagocytosis in Alzheimer disease
Brown, G. C., St George-Hyslop, P., Paolicelli, R. C., & Lemke, G. (2026) · Nature Reviews Neurology · doi:10.1038/s41582-025-01162-y · Cited by 36 · see citing works
Merrill, N. J., Davidson, W. S., He, Y., Díaz Ludovico, I., Sarkar, S., Berger, M. R., McDermott, J. E., Van Eldik, L. J., Wilcock, D. M., Monroe, M. E., et al. (2023) · Science Advances · doi:10.1126/sciadv.adi5571 · Cited by 27 · see citing works
Mole, J. P., Fasano, F., Evans, J., Sims, R., Hamilton, D. A., Kidd, E., & Metzler-Baddeley, C. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.06.014 · Cited by 20 · see citing works
Zhang, Q., Song, Q., Gu, X., Zheng, M., Wang, A., Jiang, G., Huang, M., Chen, H., Qiu, Y., Bo, B., et al. (2021) · Advanced Science · doi:10.1002/advs.202001918 · Cited by 19 · see citing works
Gal, J., Katsumata, Y., Zhu, H., Srinivasan, S., Chen, J., Johnson, L. A., Wang, W.-X., Golden, L. R., Wilcock, D. M., Jicha, G. A., et al. (2022) · The American Journal of Pathology · doi:10.1016/j.ajpath.2021.11.013 · Cited by 17 · see citing works
APOE-ε4-related differences in left thalamic microstructure in cognitively healthy adults
Mole, J. P., Fasano, F., Evans, J., Sims, R., Kidd, E., Aggleton, J. P., & Metzler-Baddeley, C. (2020) · Scientific Reports · doi:10.1038/s41598-020-75992-9 · Cited by 15 · see citing works
- Authors
- Yin, C., Ackermann, S., Ma, Z., Mohanta, S. K., Zhang, C., Li, Y., Nietzsche, S., Westermann, M., Peng, L., Hu, D., Bontha, S. V., Srikakulapu, P., Beer, M., Megens, R. T. A., Steffens, S., Hildner, M., Halder, L. D., Eckstein, H.-H., Pelisek, J., Herms, J., Roeber, S., Arzberger, T., Borodovsky, A., Habenicht, L., Binder, C. J., Weber, C., Zipfel, P. F., Skerka, C., & Habenicht, A. J. R.
- Affiliations
- German Centre for Cardiovascular Research (DE)
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
- Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten (DE)
- Jena University Hospital (DE)
- Wuhan Union Hospital (CN)
- University of Tennessee Health Science Center (US)
- University of Virginia (US)
- Maastricht University (NL)
- TUM Klinikum (DE)
- Munich Cluster for Systems Neurology (DE)
- Institut für Neuropathologie (DE)
- Alnylam Pharmaceuticals (United States) (US)
- Austrian Academy of Sciences (AT)
- Corresponding author
- Yin, Changjun
- Skerka, Christine
- ORCID
- Yin, Changjun
- Ackermann, Susanne
- Ma, Zhe
- Mohanta, Sarajo K.
- Li, Yuanfang
- Westermann, Martin
- Peng, Li
- Hu, Desheng
- Bontha, Sai Vineela
- Srikakulapu, Prasad
- Megens, Remco T. A.
- Steffens, Sabine
- Halder, Luke D.
- Eckstein, Hans-Henning
- Pelisek, Jaroslav
- Herms, Jochen
- Arzberger, Thomas
- Habenicht, Livia
- Binder, Christoph J.
- Weber, Christian
- Zipfel, Peter F.
- Skerka, Christine
- Habenicht, Andreas J. R.
- Venue
- Nature Medicine
- Published
- 2019-01-28
- Volume
- 25
- Issue
- 3
- Pages
- 496-506
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC6420126
- OpenAlex
- W2911553777
- Cited by
- 305
- References
- 64
- Citations by year
- 2026: 36 · 2025: 37 · 2024: 33 · 2023: 41 · 2022: 52 · 2021: 34 · 2020: 47 · 2019: 25
- FWCI
- 16.15
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-02-04)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion)
- PubMed Central (acceptedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- apolipoprotein E, C1q, oxidized lipids, amyloid plaques, atherosclerosis, cognitive decline, neuroinflammation, cardiovascular disease, APOE isoforms
- MeSH terms
- Mice, Knockout, ApoE, Aged, Aged, 80 and over, Animals, Antigen-Antibody Complex, Aorta, Apolipoproteins E, Brain, Carotid Arteries, Carotid Artery Diseases, Choroid Plexus, Complement Pathway, Classical, Complement C5, Female, Humans, Leukocytes, Male, Microscopy, Fluorescence, Middle Aged, Complement C1q, Amyloid beta-Peptides, Protein Isoforms, RNA, Small Interfering, Atherosclerosis, Plaque, Amyloid, Cognitive Dysfunction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
