CSF1R inhibitors induce a sex-specific resilient microglial phenotype and functional rescue in a tauopathy mouse model
Open accessAbstract
Microglia are central to pathogenesis in many neurological conditions. Drugs targeting colony-stimulating factor-1 receptor (CSF1R) to block microglial proliferation in preclinical disease models have shown mixed outcomes, thus the therapeutic potential of this approach remains unclear. Here, we show that CSF1R inhibitors given by multiple dosing paradigms in the Tg2541 tauopathy mouse model cause a sex-independent reduction in pathogenic tau and reversion of non-microglial gene expression patterns toward a normal wild type signature. Despite greater drug exposure in male mice, only female mice have functional rescue and extended survival. A dose-dependent upregulation of immediate early genes and neurotransmitter dysregulation are observed in the brains of male mice only, indicating that excitotoxicity may preclude functional benefits. Drug-resilient microglia in male mice exhibit morphological and gene expression patterns consistent with increased neuroinflammatory signaling, suggesting a mechanistic basis for sex-specific excitotoxicity. Complete microglial ablation is neither required nor desirable for neuroprotection and therapeutics targeting microglia must consider sex-dependent effects.
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?
Studies using transgenic P301STau mice report that microglial depletion reduced neurodegeneration and the accumulation of phosphorylated tau.
“In line with our findings, studies using transgenic P301STau mice report that microglial depletion reduced neurodegeneration and the accumulation of phosphorylated tau (Johnson et al., 2023; Mancuso et al., 2019; Shi et al., 2019).”
From A novel molecular class that recruits HDAC/MECP2 complexes to PU.1 motifs reduces neuroinflammation (2023) · cites this paper as Johnson et al., 2023
The Results section on pathogenic tau reports that CSF1R-inhibitor treatment reduced phosphorylated tau in P301S Tg2541 mice. But the Results section on CNS injury reports reduced plasma NfL, a marker of neuronal injury, in treated females and increased NfL in treated males under the continuous-treatment regimen. Thus, the unqualified claim that microglial depletion reduced neurodegeneration omits an important sex-dependent limitation. No page numbers are available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured
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
Neurotoxic reactive astrocytes are induced by activated microglia
Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., Bennett, M. L., Münch, A. E., Chung, W.-S., Peterson, T. C., et al. (2017) · Nature · doi:10.1038/nature21029 · Cited by 7,971 · see citing works
A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease
Keren-Shaul, H., Spinrad, A., Weiner, A., Matcovitch-Natan, O., Dvir-Szternfeld, R., Ulland, T. K., David, E., Baruch, K., Lara-Astaiso, D., Toth, B., et al. (2017) · Cell · doi:10.1016/j.cell.2017.05.018 · Cited by 5,493 · see citing works
MS-DIAL: data-independent MS/MS deconvolution for comprehensive metabolome analysis
Tsugawa, H., Čajka, T., Kind, T., Ma, Y., Higgins, B. T., Ikeda, K., Kanazawa, M., VanderGheynst, J. S., Fiehn, O., & Arita, M. (2015) · Nature Methods · doi:10.1038/nmeth.3393 · Cited by 3,423 · see citing works
Krasemann, S., Madore, C., Cialic, R., Baufeld, C., Calcagno, N., El Fatimy, R., Beckers, L., O’Loughlin, E., Xu, Y., Fanek, Z., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.08.008 · Cited by 2,979 · see citing works
NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice
Heneka, M. T., Kummer, M. P., Stutz, A., Delekate, A., Schwartz, S., Vieira-Saecker, A., Griep, A., Axt, D., Remus, A., Tzeng, T.-C., et al. (2013) · Nature · doi:10.1038/nature11729 · Cited by 2,898 · see citing works
Neurodegenerative Diseases Target Large-Scale Human Brain Networks
Seeley, W. W., Crawford, R. K., Zhou, J., Miller, B. L., & Greicius, M. D. (2009) · Neuron · doi:10.1016/j.neuron.2009.03.024 · Cited by 2,350 · see citing works
Zhang, Y., Sloan, S. A., Clarke, L. E., Caneda, C., Plaza, C. A., Blumenthal, P. D., Vogel, H., Steinberg, G. K., Edwards, M. S. B., Li, G., et al. (2016) · Neuron · doi:10.1016/j.neuron.2015.11.013 · Cited by 2,295 · see citing works
Community Structure in Time-Dependent, Multiscale, and Multiplex Networks
Mucha, P. J., Richardson, T., Macon, K., Porter, M. A., & Onnela, J.-P. (2010) · Science · doi:10.1126/science.1184819 · Cited by 2,123 · see citing works
Elmore, M. R. P., Najafi, A. R., Koike, M. A., Dagher, N. N., Spangenberg, E. E., Rice, R. A., Kitazawa, M., Matusow, B., Nguyen, H., West, B. L., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.02.040 · Cited by 1,968 · see citing works
Depletion of microglia and inhibition of exosome synthesis halt tau propagation
Asai, H., Ikezu, S., Tsunoda, S., Medalla, M., Luebke, J., Haydar, T., Wolozin, B., Butovsky, O., Kügler, S., & Ikezu, T. (2015) · Nature Neuroscience · doi:10.1038/nn.4132 · Cited by 1,591 · see citing works
NLRP3 inflammasome activation drives tau pathology
Ising, C., Venegas, C., Zhang, S., Scheiblich, H., Schmidt, S. V., Vieira-Saecker, A., Schwartz, S., Albasset, S., McManus, R. M., Tejera, D., et al. (2019) · Nature · doi:10.1038/s41586-019-1769-z · Cited by 1,487 · see citing works
Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution
Masuda, T., Sankowski, R., Staszewski, O., Böttcher, C., Amann, L., Sagar, Scheiwe, C., Nessler, S., Kunz, P., van Loo, G., et al. (2019) · Nature · doi:10.1038/s41586-019-0924-x · Cited by 1,310 · see citing works
Dong, X.-X., Wang, Y., & Qin, Z.-H. (2009) · Acta Pharmacologica Sinica · doi:10.1038/aps.2009.24 · Cited by 1,297 · see citing works
Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson’s disease
Yun, S. P., Kam, T.-I., Panicker, N., Kim, S., Oh, Y., Park, J.-S., Kwon, S.-H., Park, Y. J., Karuppagounder, S. S., Park, H., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0051-5 · Cited by 1,123 · see citing works
Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy
Cannarile, M. A., Weisser, M., Jacob, W., Jegg, A.-M., Ries, C. H., & Rüttinger, D. (2017) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-017-0257-y · Cited by 1,029 · see citing works
Distinct Tau Prion Strains Propagate in Cells and Mice and Define Different Tauopathies
Sanders, D. W., Kaufman, S. K., DeVos, S. L., Sharma, A. M., Mirbaha, H., Li, A., Barker, S. J., Foley, A. C., Thorpe, J. R., Serpell, L. C., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.04.047 · Cited by 986 · see citing works
Negative feedback control of neuronal activity by microglia
Badimon, A., Strasburger, H. J., Ayata, P., Chen, X., Nair, A., Ikegami, A., Hwang, P., Chan, A. T., Graves, S. M., Uweru, J. O., et al. (2020) · Nature · doi:10.1038/s41586-020-2777-8 · Cited by 979 · see citing works
Spangenberg, E., Severson, P. L., Hohsfield, L. A., Crapser, J., Zhang, J., Burton, E. A., Zhang, Y., Spevak, W., Lin, J., Phan, N. Y., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11674-z · Cited by 939 · see citing works
CSF-1 receptor signaling in myeloid cells.
Stanley, E. R., & Chitu, V. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a021857 · Cited by 825 · see citing works
Allen, B., Ingram, E., Takao, M., Smith, M. J., Jakes, R., Virdee, K., Yoshida, H., Holzer, M., Craxton, M., Emson, P. C., et al. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-21-09340.2002 · Cited by 746 · see citing works
Spangenberg, E. E., Lee, R. J., Najafi, A. R., Rice, R. A., Elmore, M. R. P., Blurton-Jones, M., West, B. L., & Green, K. N. (2016) · Brain · doi:10.1093/brain/aww016 · Cited by 695 · see citing works
Iba, M., Guo, J. L., McBride, J. D., Zhang, B., Trojanowski, J. Q., & Lee, V. M.-Y. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.2642-12.2013 · Cited by 664 · see citing works
Friedman, B. A., Srinivasan, K., Ayalon, G., Meilandt, W. J., Lin, H., Huntley, M. A., Cao, Y., Lee, S.-H., Haddick, P. C. G., Ngu, H., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2017.12.066 · Cited by 662 · see citing works
Domains of tau Protein and Interactions with Microtubules
Gustke, N., Trinczek, B., Biernat, J., Mandelkow, E.-M., & Mandelkow, E. (1994) · Biochemistry · doi:10.1021/bi00198a017 · Cited by 655 · see citing works
Chiu, I. M., Morimoto, E. T. A., Goodarzi, H., Liao, J. T., O’Keeffe, S., Phatnani, H. P., Muratet, M., Carroll, M. C., Levy, S., Tavazoie, S., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.06.018 · Cited by 651 · see citing works
Microglia are an essential component of the neuroprotective scar that forms after spinal cord injury
Bellver‐Landete, V., Bretheau, F., Mailhot, B., Vallières, N., Lessard, M., Janelle, M.-E., Vernoux, N., Tremblay, M., Führmann, T., Shoichet, M. S., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-08446-0 · Cited by 627 · see citing works
Maphis, N., Xu, G., Kokiko-Cochran, O. N., Jiang, S., Cardona, A., Ransohoff, R. M., Lamb, B. T., & Bhaskar, K. (2015) · Brain · doi:10.1093/brain/awv081 · Cited by 595 · see citing works
Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight
Shi, Y., & Holtzman, D. M. (2018) · Nature Reviews Immunology · doi:10.1038/s41577-018-0051-1 · Cited by 595 · see citing works
Structure-guided blockade of CSF1R kinase in tenosynovial giant-cell tumor
Tap, W. D., Wainberg, Z. A., Anthony, S. P., Ibrahim, P. N., Zhang, C., Healey, J. H., Chmielowski, B., Staddon, A. P., Cohn, A. L., Shapiro, G. I., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1411366 · Cited by 582 · see citing works
Dejanovic, B., Huntley, M. A., De Mazière, A., Meilandt, W. J., Wu, T., Srinivasan, K., Jiang, Z., Gandham, V., Friedman, B. A., Ngu, H., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.014 · Cited by 575 · see citing works
Trans-cellular Propagation of Tau Aggregation by Fibrillar Species
Kfoury, N., Holmes, B. B., Jiang, H., Holtzman, D. M., & Diamond, M. I. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.346072 · Cited by 552 · see citing works
Microglial subtypes: diversity within the microglial community
Stratoulias, V., Venero, J. L., Tremblay, M., & Joseph, B. (2019) · The EMBO Journal · doi:10.15252/embj.2019101997 · Cited by 536 · see citing works
The Lifespan and Turnover of Microglia in the Human Brain
Réu, P., Khosravi, A., Bernard, S., Mold, J. E., Salehpour, M., Alkass, K., Perl, S., Tisdale, J., Possnert, G., Druid, H., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.07.004 · Cited by 515 · see citing works
Dagher, N. N., Najafi, A. R., Kayala, K. M. N., Elmore, M. R. P., White, T. E., Medeiros, R., West, B. L., & Green, K. N. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0366-9 · Cited by 505 · see citing works
Distribution patterns of tau pathology in progressive supranuclear palsy
Kovacs, G. G., Lukic, M. J., Irwin, D. J., Arzberger, T., Respondek, G., Lee, E. B., Coughlin, D., Giese, A., Grossman, M., Kurz, C., et al. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02158-2 · Cited by 483 · see citing works
Transcriptional and Translational Differences of Microglia from Male and Female Brains
Guneykaya, D., Ivanov, A., Hernandez, D. P., Haage, V., Wojtas, B., Meyer, N., Maricos, M., Jordan, P., Buonfiglioli, A., Gielniewski, B., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.08.001 · Cited by 477 · see citing works
Frontotemporal Dementia and Corticobasal Degeneration in a Family with a P301S Mutation in Tau
Bugiani, O., Murrell, J. R., Giaccone, G., Hasegawa, M., Ghigo, G., Tabaton, M., Morbin, M., Primavera, A., Carella, F., Solaro, C., et al. (1999) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199906000-00011 · Cited by 450 · see citing works
Microglia drive APOE-dependent neurodegeneration in a tauopathy mouse model
Shi, Y., Manis, M., Long, J., Wang, K., Sullivan, P. M., Remolina Serrano, J., Hoyle, R., & Holtzman, D. M. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20190980 · Cited by 448 · see citing works
Stancu, I.-C., Cremers, N., Vanrusselt, H., Couturier, J., Vanoosthuyse, A., Kessels, S., Lodder, C., Brône, B., Huaux, F., Octave, J.-N., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-018-01957-y · Cited by 447 · see citing works
Detecting Activated Cell Populations Using Single-Cell RNA-Seq
Wu, Y. E., Pan, L., Zuo, Y., Li, X., & Hong, W. (2017) · Neuron · doi:10.1016/j.neuron.2017.09.026 · Cited by 438 · see citing works
Bacioglu, M., Maia, L. F., Preische, O., Schelle, J., Apel, A., Kaeser, S. A., Schweighauser, M., Eninger, T., Lambert, M., Pilotto, A., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.05.018 · Cited by 435 · see citing works
Tau impairs neural circuits, dominating amyloid-β effects, in Alzheimer models in vivo
Busche, M. A., Wegmann, S., Dujardin, S., Commins, C., Schiantarelli, J., Klickstein, N., Kamath, T. V., Carlson, G. A., Nelken, I., & Hyman, B. T. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0289-8 · Cited by 413 · see citing works
Sosna, J., Philipp, S., Albay, R., Reyes-Ruiz, J. M., Baglietto-Vargas, D., LaFerla, F. M., & Glabe, C. G. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0244-x · Cited by 406 · see citing works
Microglial NF-κB drives tau spreading and toxicity in a mouse model of tauopathy
Wang, C., Fan, L., Khawaja, R. R., Liu, B., Zhan, L., Kodama, L., Chin, M., Li, Y., Le, D., Zhou, Y., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29552-6 · Cited by 333 · see citing works
Lei, F., Cui, N., Zhou, C., Chodosh, J., Vavvas, D. G., & Paschalis, E. I. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1922788117 · Cited by 322 · see citing works
Matarin, M., Salih, D. A., Yasvoina, M., Cummings, D. M., Guelfi, S., Liu, W., Nahaboo Solim, M. A., Moens, T. G., Paublete, R. M., Ali, S. S., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2014.12.041 · Cited by 290 · see citing works
Neuroprotective function for ramified microglia in hippocampal excitotoxicity
Vinet, J., van Weering, H. R., Heinrich, A., Kälin, R. E., Wegner, A., Brouwer, N., Heppner, F. L., van Rooijen, N., Boddeke, H. W., & Biber, K. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-27 · Cited by 274 · see citing works
Luo, J., Elwood, F., Britschgi, M., Villeda, S., Zhang, H., Ding, Z., Zhu, L., Alabsi, H., Getachew, R., Narasimhan, R., et al. (2013) · Journal of Experimental Medicine · doi:10.1084/jem.20120412 · Cited by 262 · see citing works
Effects of frontotemporal dementia FTDP‐17 mutations on heparin‐induced assembly of tau filaments
Goedert, M., Jakes, R., & Crowther, R. A. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00508-6 · Cited by 260 · see citing works
Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau
Kang, S. S., Ebbert, M. T. W., Baker, K. E., Cook, C., Wang, X., Sens, J. P., Kocher, J.-P., Petrucelli, L., & Fryer, J. D. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20180653 · Cited by 260 · see citing works
CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice
Mancuso, R., Fryatt, G., Cleal, M., Obst, J., Pipi, E., Monzón-Sandoval, J., Ribe, E., Winchester, L., Webber, C., Nevado, A., et al. (2019) · Brain · doi:10.1093/brain/awz241 · Cited by 235 · see citing works
Elmore, M. R. P., Lee, R. J., West, B. L., & Green, K. N. (2015) · PLoS ONE · doi:10.1371/journal.pone.0122912 · Cited by 228 · see citing works
Bellucci, A., Westwood, A. J., Ingram, E., Casamenti, F., Goedert, M., & Spillantini, M. G. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63421-9 · Cited by 215 · see citing works
Ishizawa, K., & Dickson, D. W. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.6.647 · Cited by 209 · see citing works
PET imaging of microglia by targeting macrophage colony-stimulating factor 1 receptor (CSF1R)
Horti, A. G., Naik, R., Foss, C. A., Minn, I., Misheneva, V., Du, Y., Wang, Y., Mathews, W. B., Wu, Y., Hall, A., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1812155116 · Cited by 204 · see citing works
Barghorn, S., Biernat, J., & Mandelkow�, E. (2005) · Humana Press eBooks · doi:10.1385/1-59259-874-9:035 · Cited by 193 · see citing works
Exploiting microglial and peripheral immune cell crosstalk to treat Alzheimer’s disease
Dionisio-Santos, D. A., Olschowka, J. A., & O’Banion, M. K. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1453-0 · Cited by 184 · see citing works
Benner, B. N., Good, L., Quiroga, D. M., Schultz, T. E., Kassem, M. A. M., Carson, W. E., Cherian, M. A., Sardesai, S. D., & Wesolowski, R. (2020) · Drug Design Development and Therapy · doi:10.2147/dddt.s253232 · Cited by 182 · see citing works
Ashton, N. J., Leuzy, A., Lim, Y. M., Troakes, C., Hortobágyi, T., Höglund, K., Aarsland, D., Lovestone, S., Schöll, M., Blennow, K., et al. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0649-3 · Cited by 172 · see citing works
Dumont, M., Stack, C., Elipenahli, C., Jainuddin, S., Gerges, M., Starkova, N. N., Yang, L., Starkov, A. A., & Beal, F. M. (2011) · The FASEB Journal · doi:10.1096/fj.11-186650 · Cited by 139 · see citing works
Pinto, B., Morelli, G., Rastogi, M., Savardi, A., Fumagalli, A., Petretto, A., Bartolucci, M., Varea, E., Catelani, T., Contestabile, A., et al. (2020) · Neuron · doi:10.1016/j.neuron.2020.09.010 · Cited by 135 · see citing works
Aβ and tau prion-like activities decline with longevity in the Alzheimer’s disease human brain
Aoyagi, A., Condello, C., Stöhr, J., Yue, W., Rivera, B. M., Lee, J. C., Woerman, A. L., Halliday, G. M., van Duinen, S. G., Ingelsson, M., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aat8462 · Cited by 130 · see citing works
Cell-Mediated Neuroprotection in a Mouse Model of Human Tauopathy
Hampton, D. W., Webber, D. J., Bilican, B., Goedert, M., Spillantini, M. G., & Chandran, S. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0834-10.2010 · Cited by 129 · see citing works
Lee, S.-H., Le Pichon, C. E., Adolfsson, O., Gafner, V., Pihlgren, M., Lin, H., Solanoy, H., Brendza, R., Ngu, H., Foreman, O., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.06.099 · Cited by 125 · see citing works
CSF neurofilament light chain and phosphorylated tau 181 predict disease progression in PSP
Rojas, J. C., Bang, J., Lobach, I. V., Tsai, R. M., Rabinovici, G. D., Miller, B. L., Boxer, A. L., AL-108-231 Investigators, Williams, D. R., Lafontaine, A. L., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000004859 · Cited by 113 · see citing works
Do Microglial Sex Differences Contribute to Sex Differences in Neurodegenerative Diseases?
Kodama, L., & Gan, L. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.05.001 · Cited by 113 · see citing works
Bioluminescence imaging of Aβ deposition in bigenic mouse models of Alzheimer's disease
Watts, J. C., Giles, K., Grillo, S. K., Lemus, A., DeArmond, S. J., & Prusiner, S. B. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019034108 · Cited by 109 · see citing works
Microglial microRNAs mediate sex-specific responses to tau pathology
Kodama, L., Guzman, E., Etchegaray, J. I., Li, Y., Sayed, F. A., Zhou, L., Zhou, Y., Zhan, L., Le, D., Udeochu, J. C., et al. (2020) · Nature Neuroscience · doi:10.1038/s41593-019-0560-7 · Cited by 109 · see citing works
Liu, Y., Given, K. S., Dickson, E. L., Owens, G. P., Macklin, W. B., & Bennett, J. L. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.04.011 · Cited by 105 · see citing works
Colombo, G., Cubero, R. J. A., Kanari, L., Venturino, A., Schulz, R., Scolamiero, M., Agerberg, J., Mathys, H., Tsai, L.-H., Chachólski, W., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01167-6 · Cited by 100 · see citing works
Rexach, J. E., Polioudakis, D., Yin, A., Swarup, V., Chang, T. S., Nguyen, T., Sarkar, A., Chen, L., Huang, J., Lin, L.-C., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108398 · Cited by 94 · see citing works
Partial reduction of microglia does not affect tau pathology in aged mice
Bennett, R. E., Bryant, A., Hu, M., Robbins, A. B., Hopp, S. C., & Hyman, B. T. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1348-5 · Cited by 91 · see citing works
Shifting paradigms: The central role of microglia in Alzheimer’s disease
Schwabe, T., Srinivasan, K., & Rhinn, H. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104962 · Cited by 84 · see citing works
Wang, H., Li, Y., Ryder, J. W., Hole, J. T., Ebert, P. J., Airey, D. C., Qian, H.-R., Logsdon, B., Fisher, A., Ahmed, Z., et al. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0296-y · Cited by 83 · see citing works
Zhan, L., Fan, L., Kodama, L., Sohn, P., Wong, M. Y., Mousa, G. A., Zhou, Y., Li, Y., & Gan, L. (2020) · eLife · doi:10.7554/elife.51796 · Cited by 79 · see citing works
Kerkhofs, D., van Hagen, B. T. J., Milanova, I. V., Schell, K. J., van Essen, H., Wijnands, E., Goossens, P., Blankesteijn, W. M., Unger, T., Prickaerts, J., et al. (2020) · Theranostics · doi:10.7150/thno.44394 · Cited by 70 · see citing works
Hong, J., Cho, I., Kwak, K. I., Suh, E. C., Seo, J., Min, H. J., Choi, S., Kim, C., Park, S. H., Jo, E., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.132522 · Cited by 64 · see citing works
Allen, M., Wang, X., Serie, D., Strickland, S. L., Burgess, J. D., Koga, S., Younkin, C. S., Nguyen, T., Malphrus, K. G., Lincoln, S., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1900-5 · Cited by 58 · see citing works
Hyperactivity with Agitative-Like Behavior in a Mouse Tauopathy Model
Jul, P., Volbracht, C., de Jong, I. E. M., Helboe, L., Elvang, A. B., & Pedersen, J. T. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-150292 · Cited by 57 · see citing works
Liu, M., Jiang, L., Wen, M., Ke, Y., Tong, X., Huang, W., & Chen, R. (2020) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00205.2020 · Cited by 54 · see citing works
Microglial depletion and activation: A [11C]PBR28 PET study in nonhuman primates
Hillmer, A. T., Holden, D., Fowles, K., Nabulsi, N., West, B. L., Carson, R. E., & Cosgrove, K. (2017) · EJNMMI Research · doi:10.1186/s13550-017-0305-0 · Cited by 49 · see citing works
Wang, X., Smith, K. D. B., Pearson, M. S., Hughes, A. C., Cosden, M. L., Marcus, J., Hess, J. F., Savage, M. J., Rosahl, T. W., Smith, S. M., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0195486 · Cited by 35 · see citing works
Sex- and region-biased depletion of microglia/macrophages attenuates CLN1 disease in mice
Berve, K., West, B. L., Martini, R., & Groh, J. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01996-x · Cited by 27 · see citing works
Evidence for sortilin modulating regional accumulation of human tau prions in transgenic mice
Johnson, N. R., Condello, C., Guan, S., Oehler, A., Becker, J., Gavidia, M., Carlson, G. A., Giles, K., & Prusiner, S. B. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1717193114 · Cited by 26 · see citing works
Prion biology: implications for Alzheimer's disease therapeutics
Condello, C., DeGrado, W. F., & Prusiner, S. B. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30274-x · Cited by 19 · see citing works
Tau impairs neural circuits, dominating amyloid-beta effects, in Alzheimer models in vivo
Busche, M., Wegmann, S., Dujardin, S., Commins, C., Schiantarelli, J., Klickstein, N., Kamath, T., Carlson, G., Nelken, I., & Hyman, B. (2019) · UCL Discovery (University College London) · Cited by 4 · see citing works
Sperfeld (1999) · Pure Amsterdam UMC · doi:10.1002/1531-8249(199911)46:5 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Microglia-Astrocyte Communication in Alzheimer’s Disease
Wu, Y., & Eisel, U. L. M. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230199 · Cited by 118 · see citing works
Toader, C., Tătaru, C. P., Munteanu, O., Șerban, M., Covache-Busuioc, R.-A., Ciurea, A. V., & Enyedi, M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252312613 · Cited by 106 · see citing works
Neuroimmune crosstalk in chronic neuroinflammation: microglial interactions and immune modulation
Müller, L., & Benedetto, S. D. (2025) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2025.1575022 · Cited by 90 · see citing works
de Vries, L. E., Huitinga, I., Kessels, H. W. H. G., Swaab, D. F., & Verhaagen, J. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00719-7 · Cited by 82 · see citing works
Zhang, X., Li, H., Gu, Y., Ping, A., Chen, J., Qia, Z., Xu, Z., Wang, J., Tang, S., Wang, R., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-58254-y · Cited by 72 · see citing works
The Landscape of SPP1 + Macrophages Across Tissues and Diseases: A Comprehensive Review
Palma, A. (2025) · Immunology · doi:10.1111/imm.13952 · Cited by 64 · see citing works
A novel molecular class that recruits HDAC/MECP2 complexes to PU.1 motifs reduces neuroinflammation
Ralvenius, W. T., Mungenast, A. E., Woolf, H., Huston, M. M., Gillingham, T. Z., Godin, S. K., Penney, J., Cam, H. P., Gao, F., Fernandez, C. G., et al. (2023) · Journal of Experimental Medicine · doi:10.1084/jem.20222105 · Cited by 31 · see citing works
Single-cell sequencing of the substantia nigra reveals microglial activation in a model of MPTP
Liu, Q., Liu, Z., Xie, W., Li, Y., Wang, H., Zhang, S., Wang, W., Hao, J., Geng, D., Yang, J., et al. (2024) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2024.1390310 · Cited by 20 · see citing works
Bobotis, B. C., Halvorson, T., Carrier, M., & Tremblay, M. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1317125 · Cited by 21 · see citing works
Niche-specific therapeutic targeting of myeloid cells in the central nervous system
Frosch, M., & Prinz, M. (2025) · Immunity · doi:10.1016/j.immuni.2025.03.016 · Cited by 17 · see citing works
A case for seeking sex-specific treatments in Alzheimer’s disease
Lynch, M. A. (2024) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2024.1346621 · Cited by 14 · see citing works
Henningfield, C. M., Soni, N., Lee, R. W., Sharma, R. B., Cleland, J. L., & Green, K. N. (2024) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01470-3 · Cited by 14 · see citing works
Norrie, J. L., Lupo, M. S., Little, D. R., Shirinifard, A., Mishra, A., Zhang, Q., Geiger, N., Putnam, D. K., Djekidel, M. N., Ramirez, C. A., et al. (2023) · Developmental Cell · doi:10.1016/j.devcel.2024.12.014 · Cited by 14 · see citing works
Exploring microglial replacement: From disease models to clinical translation
Zhou, K., Wang, Y., Xu, Y., Zhang, Y., & Zhu, C. (2025) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.06.011 · Cited by 13 · see citing works
Piccioni, G., Maisto, N., d’Ettorre, A., Strimpakos, G., Nisticò, R., Triaca, V., & Mango, D. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-03019-2 · Cited by 13 · see citing works
Strackeljan, L., Baidoe‐Ansah, D., Mirzapourdelavar, H., Jia, S., Kaushik, R., Cangalaya, C., & Dityatev, A. E. (2025) · Experimental Neurology · doi:10.1016/j.expneurol.2025.115186 · Cited by 14 · see citing works
Le, L., Eliseeva, S. I., Plunk, E. C., Kara-Pabani, K., Li, H., Yarovinsky, F., & Majewska, A. K. (2025) · Cell Reports · doi:10.1016/j.celrep.2024.115176 · Cited by 12 · see citing works
Bhatia, T. N., Jamenis, A. S., Abbas, M., Clark, R. N., Miner, K. M., Chandwani, M. N., Kim, R. E., Hilinski, W. C., O’Donnell, L. A., Luk, K. C., et al. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106196 · Cited by 11 · see citing works
Holmes, B. B., Weigel, T. K., Chung, J. M., Kaufman, S. K., Apresa, B. I., Byrnes, J. R., Kumru, K. S., Vaquer‐Alicea, J., Gupta, A., Rose, I. V. L., et al. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00883-4 · Cited by 13 · see citing works
Expansion and pathogenic activation of skeletal muscle–resident macrophages in mdx5cv/Ccr2−/− mice
Wang, Y.-H., Wang, X., Alabdullatif, S., Homma, S. T., Alekseyev, Y. O., & Zhou, L. (2025) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.2410095122 · Cited by 13 · see citing works
Twenty years of therapeutic development in tauopathy mouse models: a scoping review
Langness, V. F., Simmons, D. A., McHugh, T. L. M., Butler, R. R., Zhou, J., Liu, H., Yang, T., Ellerby, L., & Longo, F. M. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70578 · Cited by 9 · see citing works
Cao, K., Cheng, W., Qiu, L., Wang, Z., Zhao, Y., Yuan, Y., Wu, W., Xue, J., Zeng, L., Wu, Z.-Y., et al. (2026) · Neuron · doi:10.1016/j.neuron.2025.12.044 · Cited by 12 · see citing works
Zattoni, M., Bernegger, S., Weinbender, S., Altendorfer, B., Mrowetz, H., Benedetti, A., Poupardin, R., Unger, M. S., & Aigner, L. (2025) · Scientific Reports · doi:10.1038/s41598-025-22137-5 · Cited by 7 · see citing works
Chakif, D., & Furrer, J. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1765786 · Cited by 9 · see citing works
Modulation of recovery from neonatal hyperoxic lung injury by sex as a biological variable
Cantu, A., Gutierrez, M. E. C., Dong, X., Leek, C. C., Anguera, M. C., & Lingappan, K. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102933 · Cited by 7 · see citing works
Taylor, I., Patkar, O. L., Liu, Y., Jacquelin, S., Green, E. K., Ranpura, G. N., Carter‐Cusack, D., Rosendahl, N., Ewing, A. D., Kurniawan, N. D., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.16.633478 · Cited by 6 · see citing works
Ferreira, A. F. F., Santos-Silva, A. C., Muratori, B. G., & Britto, L. R. G. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1733682 · Cited by 5 · see citing works
Scott, L., Winzey, K. D., Moreira, D., Bresee, C. J., Vit, J., Tourtellotte, W. G., Karumanchi, S. A., & Lahiri, S. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03260-y · Cited by 5 · see citing works
Plasma neurofilament light reflects more severe manifestation of Alzheimer’s disease in men
Cheng, X.-Q., Wang, Z.-H., He, K., Xia, Y., Wang, Y., Guo, Q.-H., Xie, F., & Yuan, P. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03149-z · Cited by 4 · see citing works
Chen, F., Wang, H., Liu, Y., Liu, Q., Yang, S., Ma, Z., & Yuan, Y. (2025) · Theriogenology · doi:10.1016/j.theriogenology.2025.117756 · Cited by 4 · see citing works
Seifinejad, A., Bandarabadi, M., Haddar, M., Wundt, S., Tafti, M., Vassalli, A., Khani, A., & Monaco, G. (2025) · Communications Biology · doi:10.1038/s42003-025-08781-7 · Cited by 3 · see citing works
Wang, S., Wang, Y., Strehle, J., Wernersbach, I., Papakonstantinou, E., Somnuke, P., Ritter, K., Klein, M., Tegeder, I., & Schäfer, M. K. E. (2025) · Neurotherapeutics · doi:10.1016/j.neurot.2025.e00787 · Cited by 3 · see citing works
Sharma, A., & Singh, T. G. (2026) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2026.104097 · Cited by 5 · see citing works
Gauer, C., Battis, K., Schneider, Y., Florio, J. B., Mante, M., Kim, H. Y., Rissman, R. A., Hoffmann, A., & Winkler, J. (2024) · Experimental Neurology · doi:10.1016/j.expneurol.2024.114706 · Cited by 3 · see citing works
Ayoub, R., Yang, S., Ji, H., Fan, L., Michino, S. D. D., Mabbott, D., & Nieman, B. J. (2024) · NMR in Biomedicine · doi:10.1002/nbm.5222 · Cited by 2 · see citing works
Cheng, X., Zhao, R., Qiu, H., Song, P., Kou, L., Sang, S., Xia, Y., Cai, W., Jin, B., Huang, Q., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.18.613405 · Cited by 2 · see citing works
iS2C2: a cointelligent platform for mechanistic discovery of disease cellular crosstalk
Sheng, J., Ahn, J. Y., Yang, L., Wan, Z., Qi, S., Yu, X., Xu, Z., Cao, Y., Vasquez, M., Irfan, A., et al. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02691-8 · Cited by 1 · see citing works
Gong, N.-N., Qin, G.-M., Sun, J.-X., Shen, S.-Y., Zhang, X.-X., & Lu, M.-M. (2026) · Clinical and Translational Oncology · doi:10.1007/s12094-026-04370-0 · Cited by 1 · see citing works
Modeling Taupathies in Zebrafish (Danio rerio)
Kotova, M. M., Kolesnikova, T. O., & Kalueff, A. V. (2023) · Российский физиологический журнал им И М Сеченова · doi:10.31857/s0869813923110067 · Cited by 1 · see citing works
The role of immune cells in brain injuries and diseases
Shi, Y., Stowe, A. M., & Hu, X. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106340 · Cited by 1 · see citing works
Modeling Tauopathies in Zebrafish (Danio rerio)
Kotova, M. M., Kolesnikova, T. O., & Kalueff, A. V. (2023) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093023060133
Le, L., Eliseeva, S. I., Kara-Pabani, K., Li, H., Yarovinsky, F., & Majewska, A. K. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4795163
Li, R., Fan, J.-Q., & Lin, B. (2026) · Science Advances · doi:10.1126/sciadv.aea6467
Xia, Y., Yuan, P., Fei, G., & Cheng, X. (2026) · Brain medicine : · doi:10.61373/bm026y.0051
Human Stem Cell-Derived Models of the Alzheimer’s Disease Neuroimmune System
Summers, R., Quang, D., & Johnson, N. R. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27167360 · Cited by 1 · see citing works
Beganovic, A., Flotho, M., Li, J., Guldner, I. H., Reich, M., Wahl, V., Graf, S., Donate, P., Rishik, S., Dashdorj, E. D., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.03.745468
- Authors
- Johnson, N. R., Yuan, P., Castillo, E., Lopez, T. P., Yue, W., Bond, A., Rivera, B. M., Sullivan, M. C., Hirouchi, M., Giles, K., Aoyagi, A., & Condello, C.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Condello, Carlo
- ORCID
- Venue
- Nature Communications
- Published
- 2023-01-09
- Volume
- 14
- Issue
- 1
- Pages
- 118-118
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC9829908
- OpenAlex
- W4313829033
- Cited by
- 46
- References
- 86
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 12 · 2023: 8
- FWCI
- 4.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Natural Science Foundation of Shanghai (22ZR1415000)
- U.S. Department of Health & Human Services | NIH | National Institute on Aging (RF1 AG061874, P01 AG002132)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- CSF1R inhibitor, microglia, tauopathy, sex differences, excitotoxicity, neuroinflammation, microglial phenotype, neuroprotection, neurotransmitter dysregulation, immediate early genes, microglial ablation, neurodegeneration
- MeSH terms
- Animals, Brain, Disease Models, Animal, Female, Male, Phenotype, Receptors, Colony-Stimulating Factor, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor, Microglia, Tauopathies, Mice
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
