Microglial phagocytosis in Alzheimer disease
Abstract
Accumulating evidence indicates that Alzheimer disease (AD) is caused by dysregulated microglial phagocytosis. The main risk factor for AD is age, and ageing reduces microglial phagocytosis of amyloid-β (Aβ) plaques, while increasing microglial phagocytosis of synapses and neurons. Most of the known genetic risk for AD can be linked to microglial phagocytosis, including ABCA1, ABI3, ACE, ADAM17, APOE, APP, BIN1, BLNK, CD2AP, CD33, CLU, CR1, CTSB, CTSH, EED, GRN, INPP5D, LILRB2, PICALM, PLCG2, PSEN1, PTK2B, SIGLEC11, SORL1, SPI1, TMEM106B and TREM2. Moreover, the only disease-modifying treatments for AD - anti-Aβ antibodies - work by increasing microglial phagocytosis of Aβ aggregates. Microglial phagocytosis of Aβ via TREM2, LRP1, CD33, TAM receptors and anti-Aβ antibodies appears to reduce AD pathology by pruning and compacting plaques, restricting subsequent tau pathology, whereas microglial phagocytosis of synapses and neurons seems detrimental in the later stages of AD, via complement, P2Y 6 receptor and TREM2. However, the roles of microglial phagocytosis in AD are complex and multifaceted, and improved treatments are likely to require a deeper understanding of these roles.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Cites
Lecanemab in early Alzheimer's disease
van Dyck, C. H., Swanson, C. J., Aisen, P., Bateman, R. J., Chen, C., Gee, M., Kanekiyo, M., Li, D., Reyderman, L., Cohen, S., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2212948 · Cited by 5,678 · 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
Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
Ginhoux, F., Greter, M., Leboeuf, M., Nandi, S., See, P., Gokhan, S., Mehler, M. F., Conway, S. J., Ng, L. G., Stanley, E. R., et al. (2010) · Science · doi:10.1126/science.1194637 · Cited by 5,175 · see citing works
Terry, R. D., Masliah, E., Salmon, D. P., Butters, N., DeTeresa, R., Hill, R., Hansen, L. A., & Katzman, R. (1991) · Annals of Neurology · doi:10.1002/ana.410300410 · Cited by 4,397 · see citing works
Synaptic Pruning by Microglia Is Necessary for Normal Brain Development
Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., Giustetto, M., Ferreira, T. A., Guiducci, E., Dumas, L., et al. (2011) · Science · doi:10.1126/science.1202529 · Cited by 4,244 · see citing works
Self-citationMicroglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner
Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A., & Stevens, B. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.026 · Cited by 4,089 · see citing works
Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease
Sherrington, R., Rogaev, E. I., Liang, Y., Rogaeva, E. A., Levesque, G., Ikeda, M., Chi, H., Lin, C., Li, G., Holman, K., et al. (1995) · Nature · doi:10.1038/375754a0 · Cited by 4,051 · see citing works
Self-citationAssociation of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease
Saunders, A. M., Strittmatter, W. J., Schmechel, D., St. George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., Gusella, J. F., Crapper-MacLachlan, D. R., Alberts, M. J., et al. (1993) · Neurology · doi:10.1212/wnl.43.8.1467 · Cited by 3,786 · see citing works
Self-citationComplement 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 · cited 5× · see citing works
“In mice, injection of oligomeric Aβ into the lateral ventricles upregulated complement and microglial engulfment of postsynaptic structures 50 .”
Influential<i>TREM2</i> Variants in Alzheimer's Disease
Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211851 · Cited by 3,020 · see citing works
Self-citationKrasemann, 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
Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial
Sims, J. R., Zimmer, J. A., Evans, C. D., Lu, M., Ardayfio, P., Sparks, J., Wessels, A. M., Shcherbinin, S., Wang, H., Monkul Nery, E. S., et al. (2023) · JAMA · doi:10.1001/jama.2023.13239 · Cited by 2,932 · see citing works
Knopman, D. S., Amieva, H., Petersen, R. C., Chételat, G., Holtzman, D. M., Hyman, B. T., Nixon, R. A., & Jones, D. T. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-021-00269-y · Cited by 2,606 · see citing works
New insights into the genetic etiology of Alzheimer’s disease and related dementias
Bellenguez, C., Küçükali, F., Jansen, I. E., Kleineidam, L., Moreno-Grau, S., Amin, N., Naj, A. C., Campos-Martin, R., Grenier-Boley, B., Andrade, V., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01024-z · Cited by 2,498 · see citing works
Hammond, T. R., Dufort, C., Dissing-Olesen, L., Giera, S., Young, A., Wysoker, A., Walker, A. J., Segel, M., Nemesh, J., Saunders, A., et al. (2018) · doi:10.1101/406140 · Cited by 2,225 · see citing works
Microglia states and nomenclature: A field at its crossroads
Paolicelli, R. C., Sierra, A., Stevens, B., Tremblay, M.-E., Aguzzi, A., Ajami, B., Amit, I., Audinat, E., Bechmann, I., Bennett, M., et al. (2022) · Neuron · doi:10.1016/j.neuron.2022.10.020 · Cited by 1,973 · see citing works
Self-citationTREM2 Lipid Sensing Sustains the Microglial Response in an Alzheimer’s Disease Model
Wang, Y., Cella, M., Mallinson, K., Ulrich, J. D., Young, K. L., Robinette, M. L., Gilfillan, S., Krishnan, G. M., Sudhakar, S., Zinselmeyer, B. H., et al. (2015) · Cell · doi:10.1016/j.cell.2015.01.049 · Cited by 1,736 · 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
Microglia Biology: One Century of Evolving Concepts
Prinz, M., Jung, S., & Priller, J. (2019) · Cell · doi:10.1016/j.cell.2019.08.053 · Cited by 1,525 · see citing works
Marschallinger, J., Iram, T., Zardeneta, M., Lee, S. E., Lehallier, B., Haney, M. S., Pluvinage, J. V., Mathur, V., Hahn, O., Morgens, D. W., et al. (2020) · Nature Neuroscience · doi:10.1038/s41593-019-0566-1 · Cited by 1,384 · cited 2× · see citing works
“In addition to the states described above, ‘lipid-droplet-accumulating microglia’ are found in the brains of aged mice and older people and are characterized by decreased phagocytosis and increased secretion of inflammatory cytokines 32 .”
Zhou, Y., Song, W. M., Andhey, P. S., Swain, A., Levy, T., Miller, K. R., Poliani, P. L., Cominelli, M., Grover, S., Gilfillan, S., et al. (2020) · Nature Medicine · doi:10.1038/s41591-019-0695-9 · Cited by 1,150 · see citing works
Li, Q., Cheng, Z., Zhou, L., Darmanis, S., Neff, N. F., Okamoto, J., Gulati, G., Bennett, M. L., Sun, L. O., Clarke, L. E., et al. (2019) · Neuron · doi:10.1016/j.neuron.2018.12.006 · Cited by 1,129 · see citing works
ARUK Consortium, Sims, R., GERAD/PERADES, C., van der Lee, S. J., Naj, A. C., Bellenguez, C., Badarinarayan, N., Jakobsdottir, J., Kunkle, B. W., Boland, A., et al. (2017) · Nature Genetics · doi:10.1038/ng.3916 · Cited by 1,126 · see citing works
Self-citationLin, Y.-T., Seo, J., Gao, F., Feldman, H. M., Wen, H.-L., Penney, J., Cam, H. P., Gjoneska, E., Raja, W. K., Cheng, J., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.05.008 · Cited by 1,125 · see citing works
Intraneuronal Aβ42 Accumulation in Human Brain
Gouras, G. K., Tsai, J., Naslund, J., Vincent, B., Edgar, M., Checler, F., Greenfield, J. P., Haroutunian, V., Buxbaum, J. D., Xu, H., et al. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64700-1 · Cited by 991 · see citing works
Yeh, F. L., Wang, Y., Tom, I., Gonzalez, L. C., & Sheng, M. (2016) · Neuron · doi:10.1016/j.neuron.2016.06.015 · Cited by 943 · 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
Microglial Phagocytosis of Live Neurons
Brown, G. C., & Neher, J. J. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3710 · Cited by 853 · see citing works
Self-citationBrain cell type–specific enhancer–promoter interactome maps and disease <b>-</b> risk association
Nott, A., Holtman, I. R., Coufal, N. G., Schlachetzki, J. C. M., Yu, M., Hu, R., Han, C. Z., Pena, M., Xiao, J., Wu, Y., et al. (2019) · Science · doi:10.1126/science.aay0793 · Cited by 823 · see citing works
Complement activation by beta-amyloid in Alzheimer disease.
Rogers, J., Cooper, N. R., Webster, S., Schultz, J., McGeer, P. L., Styren, S. D., Civin, W. H., Brachova, L., Bradt, B., & Ward, P. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.21.10016 · Cited by 817 · see citing works
UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis
Koizumi, S., Shigemoto-Mogami, Y., Nasu-Tada, K., Shinozaki, Y., Ohsawa, K., Tsuda, M., Joshi, B. V., Jacobson, K. A., Kohsaka, S., & Inoue, K. (2007) · Nature · doi:10.1038/nature05704 · Cited by 802 · see citing works
Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction
Weinhard, L., di Bartolomei, G., Bolasco, G., Machado, P., Schieber, N. L., Neniskyte, U., Exiga, M., Vadisiute, A., Raggioli, A., Schertel, A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03566-5 · Cited by 790 · see citing works
TREM2 Is a Receptor for β-Amyloid that Mediates Microglial Function
Zhao, Y., Wu, X., Li, X., Jiang, L.-L., Gui, X., Liu, Y., Sun, Y., Zhu, B., Piña-Crespo, J. C., Zhang, M., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.01.031 · Cited by 763 · see citing works
Lui, H., Zhang, J., Makinson, S. R., Cahill, M. K., Kelley, K. W., Huang, H.-Y., Shang, Y., Oldham, M. C., Martens, L. H., Gao, F., et al. (2016) · Cell · doi:10.1016/j.cell.2016.04.001 · Cited by 729 · see citing works
Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer’s disease
Olah, M., Menon, V., Habib, N., Taga, M. F., Ma, Y., Yung, C. J., Cimpean, M., Khairallah, A., Coronas-Samano, G., Sankowski, R., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19737-2 · Cited by 722 · see citing works
Microglia constitute a barrier that prevents neurotoxic protofibrillar Aβ42 hotspots around plaques
Condello, C., Yuan, P., Schain, A., & Grutzendler, J. (2015) · Nature Communications · doi:10.1038/ncomms7176 · Cited by 718 · 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
Paresce, D. M., Ghosh, R. N., & Maxfield, F. R. (1996) · Neuron · doi:10.1016/s0896-6273(00)80187-7 · Cited by 663 · see citing works
Neuroinflammation in Alzheimer disease
Heneka, M. T., van der Flier, W. M., Jessen, F., Hoozemanns, J., Thal, D. R., Boche, D., Brosseron, F., Teunissen, C., Zetterberg, H., Jacobs, A. H., et al. (2025) · Nature Reviews Immunology · doi:10.1038/s41577-024-01104-7 · Cited by 638 · see citing works
Self-citationTAM receptors regulate multiple features of microglial physiology
Fourgeaud, L., Través, P. G., Tufail, Y., Leal-Bailey, H., Lew, E. D., Burrola, P. G., Callaway, P., Zagórska, A., Rothlin, C. V., Nimmerjahn, A., et al. (2016) · Nature · doi:10.1038/nature17630 · Cited by 600 · see citing works
Self-citationLemke, G. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a009076 · Cited by 598 · see citing works
Self-citationApolipoprotein E Is a Ligand for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)
Atagi, Y., Liu, C.-C., Painter, M. M., Chen, X.-F., Verbeeck, C., Zheng, H., Li, X., Rademakers, R., Kang, S. S., Xu, H., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.679043 · Cited by 587 · see citing works
CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology
Initiative, T. A. D. N., Bradshaw, E. M., Chibnik, L. B., Keenan, B. T., Ottoboni, L., Raj, T., Tang, A., Rosenkrantz, L. L., Imboywa, S., Lee, M., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3435 · Cited by 570 · see citing works
Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease
Fuhrmann, M., Bittner, T., Jung, C. K. E., Burgold, S., Page, R. M., Mitteregger, G., Haass, C., LaFerla, F. M., Kretzschmar, H., & Herms, J. (2010) · Nature Neuroscience · doi:10.1038/nn.2511 · Cited by 562 · see citing works
Verghese, P. B., Castellano, J. M., Garai, K., Wang, Y., Jiang, H., Shah, A., Bu, G., Frieden, C., & Holtzman, D. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1220484110 · Cited by 556 · see citing works
Olmos-Alonso, A., Schetters, S. T. T., Sri, S., Askew, K., Mancuso, R., Vargas-Caballero, M., Holscher, C., Perry, V. H., & Gomez-Nicola, D. (2016) · Brain · doi:10.1093/brain/awv379 · Cited by 532 · see citing works
ABC1 promotes engulfment of apoptotic cells and transbilayer redistribution of phosphatidylserine.
Hamon, Y., Broccardo, C., Chambenoit, O., Luciani, M., Toti, F., Chaslin, S., Freyssinet, J., Devaux, P. F., McNeish, J. D., Marguet, D., et al. (2000) · Nature Cell Biology · doi:10.1038/35017029 · Cited by 529 · see citing works
Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex
Sipe, G. O., Lowery, Tremblay, M.-È., Kelly, E. A., Lamantia, C. E., & Majewska, A. K. (2016) · Nature Communications · doi:10.1038/ncomms10905 · Cited by 512 · see citing works
Synaptic degeneration in Alzheimer disease
Tzioras, M., McGeachan, R. I., Durrant, C. S., & Spires-Jones, T. L. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-022-00749-z · Cited by 504 · see citing works
Microglia use TAM receptors to detect and engulf amyloid β plaques
Huang, Y., Happonen, K. E., Burrola, P. G., O’Connor, C., Hah, N., Huang, L., Nimmerjahn, A., & Lemke, G. (2021) · Nature Immunology · doi:10.1038/s41590-021-00913-5 · Cited by 483 · see citing works
Self-citationTREM2 drives microglia response to amyloid-β via SYK-dependent and -independent pathways
Wang, S., Sudan, R., Peng, V., Zhou, Y., Du, S., Yuede, C. M., Lei, T., Hou, J., Cai, Z., Cella, M., et al. (2022) · Cell · doi:10.1016/j.cell.2022.09.033 · Cited by 471 · see citing works
Self-citationHuman microglial state dynamics in Alzheimer’s disease progression
Sun, N., Victor, M. B., Park, Y. P., Xiong, X., Scannail, A. N., Leary, N., Prosper, S., Viswanathan, S., Luna, X., Boix, C. A., et al. (2023) · Cell · doi:10.1016/j.cell.2023.08.037 · Cited by 462 · see citing works
CD22 blockade restores homeostatic microglial phagocytosis in ageing brains
Pluvinage, J. V., Haney, M. S., Smith, B. A. H., Sun, J., Iram, T., Bonanno, L., Li, L., Lee, D. P., Morgens, D. W., Yang, A. C., et al. (2019) · Nature · doi:10.1038/s41586-019-1088-4 · Cited by 459 · cited 1× · see citing works
“150), increased expression of retrotransposon LINE-1 (ref.”
Disease Progression-Dependent Effects of TREM2 Deficiency in a Mouse Model of Alzheimer's Disease
Jay, T. R., Hirsch, A. M., Broihier, M. L., Miller, C. M., Neilson, L. E., Ransohoff, R. M., Lamb, B. T., & Landreth, G. E. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.2110-16.2016 · Cited by 457 · see citing works
The endotoxin hypothesis of neurodegeneration
Brown, G. C. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1564-7 · Cited by 457 · 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
Distinct amyloid-β and tau-associated microglia profiles in Alzheimer’s disease
Gerrits, E., Brouwer, N., Kooistra, S. M., Woodbury, M. E., Vermeiren, Y., Lambourne, M., Mulder, J., Kummer, M., Möller, T., Biber, K., et al. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02263-w · Cited by 441 · see citing works
Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia
Scott‐Hewitt, N., Perrucci, F., Morini, R., Erreni, M., Mahoney, M., Witkowska, A., Carey, A. E., Faggiani, E., Schuetz, L. T., Mason, S., et al. (2020) · The EMBO Journal · doi:10.15252/embj.2020105380 · Cited by 425 · see citing works
Microglia Mediate the Clearance of Soluble Aβ through Fluid Phase Macropinocytosis
Mandrekar, S., Jiang, Q., Lee, C. Y. D., Koenigsknecht-Talboo, J., Holtzman, D. M., & Landreth, G. E. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5572-08.2009 · Cited by 415 · see citing works
Formation and maintenance of Alzheimer's disease β-amyloid plaques in the absence of microglia
Grathwohl, S. A., Kälin, R. E., Bolmont, T., Prokop, S., Winkelmann, G., Kaeser, S. A., Odenthal, J., Radde, R., Eldh, T., Gandy, S., et al. (2009) · Nature Neuroscience · doi:10.1038/nn.2432 · Cited by 401 · see citing works
Lee, C. Y. D., Daggett, A., Gu, X., Jiang, L.-L., Langfelder, P., Li, X., Wang, N., Zhao, Y., Park, C. S., Cooper, Y., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.02.002 · Cited by 396 · see citing works
Colonna, M. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-023-00837-1 · Cited by 394 · see citing works
TREM2 Acts Downstream of CD33 in Modulating Microglial Pathology in Alzheimer's Disease
Griciuc, A., Patel, S., Federico, A. N., Choi, S. H., Innes, B. J., Oram, M. K., Cereghetti, G., McGinty, D., Anselmo, A., Sadreyev, R. I., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.06.010 · Cited by 378 · see citing works
Inhibition of Microglial Phagocytosis Is Sufficient To Prevent Inflammatory Neuronal Death
Neher, J. J., Neniskyte, U., Zhao, J.-W., Bal-Price, A., Tolkovsky, A. M., & Brown, G. C. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003600 · Cited by 373 · see citing works
Self-citationComplement<i>C3</i>-Deficient Mice Fail to Display Age-Related Hippocampal Decline
Shi, Q., Colodner, K. J., Matousek, S. B., Merry, K., Hong, S., Kenison, J. E., Frost, J. L., Le, K. X., Li, S., Dodart, J.-C., et al. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.1698-15.2015 · Cited by 368 · see citing works
Transcriptional signature in microglia associated with Aβ plaque phagocytosis
Grubman, A., Choo, X. Y., Chew, G., Ouyang, J. F., Sun, G., Croft, N. P., Rossello, F. J., Simmons, R., Buckberry, S., Landin, D. V., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23111-1 · Cited by 357 · see citing works
Boza-Serrano, A., Ruiz, R., Sanchez-Varo, R., García-Revilla, J., Yang, Y., Jimenez-Ferrer, I., Paulus, A., Wennström, M., Vilalta, A., Allendorf, D., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02013-z · Cited by 357 · see citing works
Self-citationAlzheimer's disease: From immunotherapy to immunoprevention
Jucker, M., & Walker, L. C. (2023) · Cell · doi:10.1016/j.cell.2023.08.021 · Cited by 353 · see citing works
Dejanovic, B., Wu, T., Tsai, M.-C., Graykowski, D., Gandham, V. D., Rose, C. M., Bakalarski, C. E., Ngu, H., Wang, Y., Pandey, S., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00281-1 · Cited by 341 · see citing works
Microglia in Alzheimer's disease at single-cell level. Are there common patterns in humans and mice?
Chen, Y., & Colonna, M. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20202717 · Cited by 339 · see citing works
Wang, C., Xiong, M., Gratuze, M., Bao, X., Shi, Y., Andhey, P. S., Manis, M., Schroeder, C., Yin, Z., Madore, C., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.03.024 · Cited by 334 · see citing works
Microglia Actively remodel adult hippocampal neurogenesis through the phagocytosis secretome
Diaz-Aparicio, I., Paris, I., Sierra-Torre, V., Plaza-Zabala, A., Rodríguez-Iglesias, N., Márquez-Ropero, M., Beccari, S., Huguet, P., Abiega, O., Alberdi, E., et al. (2020) · The Journal of Neuroscience · doi:10.1523/jneurosci.0993-19.2019 · Cited by 333 · see citing works
Self-citationTREM2 function impedes tau seeding in neuritic plaques
Leyns, C. E. G., Gratuze, M., Narasimhan, S., Jain, N., Koscal, L. J., Jiang, H., Manis, M., Colonna, M., Lee, V. M. Y., Ulrich, J. D., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0433-0 · Cited by 332 · see citing works
Non-Fc-Mediated Mechanisms Are Involved in Clearance of Amyloid-β<i>In Vivo</i>by Immunotherapy
Bacskai, B. J., Kajdasz, S. T., McLellan, M. E., Games, D., Seubert, P., Schenk, D., & Hyman, B. T. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-18-07873.2002 · Cited by 323 · see citing works
GABA-Receptive Microglia Selectively Sculpt Developing Inhibitory Circuits
Favuzzi, E., Huang, S., Saldi, G.-A., Binan, L., Ibrahim, L. A., Fernández-Otero, M., Cao, Y., Zeine, A., Sefah, A., Zheng, K., et al. (2020) · Cell · doi:10.1016/j.cell.2021.06.018 · Cited by 321 · see citing works
Humanized TREM2 mice reveal microglia-intrinsic and -extrinsic effects of R47H polymorphism
Song, W. M., Joshita, S., Zhou, Y., Ulland, T. K., Gilfillan, S., & Colonna, M. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20171529 · Cited by 305 · see citing works
ApoE attenuates unresolvable inflammation by complex formation with activated C1q
Yin, C., Ackermann, S., Ma, Z., Mohanta, S. K., Zhang, C., Li, Y., Nietzsche, S., Westermann, M., Peng, L., Hu, D., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0336-8 · Cited by 305 · see citing works
Trem2 restrains the enhancement of tau accumulation and neurodegeneration by β-amyloid pathology
Lee, S.-H., Meilandt, W. J., Xie, L., Gandham, V. D., Ngu, H., Barck, K. H., Rezzonico, M. G., Imperio, J., Lalehzadeh, G., Huntley, M. A., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.02.010 · Cited by 300 · see citing works
Bemiller, S. M., McCray, T. J., Allan, K., Formica, S. V., Xu, G., Wilson, G., Kokiko-Cochran, O. N., Crish, S. D., Lasagna-Reeves, C. A., Ransohoff, R. M., et al. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0216-6 · Cited by 299 · see citing works
De Schepper, S., Ge, J. Z., Sierksma, A., Crowley, G., Ferreira, L. S. S., Garceau, D., Toomey, C. E., Sokolova, D., Rueda-Carrasco, J., Shin, S.-H., et al. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01257-z · Cited by 295 · see citing works
Microglial phagocytosis of neurons in neurodegeneration, and its regulation
Butler, C. A., Popescu, A. S., Kitchener, E. J. A., Allendorf, D. H., Puigdellívol, M., & Brown, G. C. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15327 · Cited by 293 · see citing works
Self-citationThe role of microglia in processing and spreading of bioactive tau seeds in Alzheimer’s disease
Hopp, S. C., Lin, Y., Oakley, D., Roe, A. D., DeVos, S. L., Hanlon, D., & Hyman, B. T. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1309-z · Cited by 286 · see citing works
The extracellular chaperone clusterin sequesters oligomeric forms of the amyloid-β1−40 peptide
Narayan, P. S., Orte, Á., Clarke, R. W., Bolognesi, B., Hook, S., Ganzinger, K. A., Meehan, S., Wilson, M. R., Dobson, C. M., & Klenerman, D. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2191 · Cited by 282 · see citing works
Neuronal Clearance of Amyloid-β by Endocytic Receptor LRP1
Kanekiyo, T., Cirrito, J. R., Liu, C.-C., Shinohara, M., Li, J., Schuler, D. R., Shinohara, M., Holtzman, D. M., & Bu, G. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.3487-13.2013 · Cited by 280 · see citing works
Païdassi, H., Tacnet‐Delorme, P., Garlatti, V., Darnault, C., Ghebrehiwet, B., Gaboriaud, C., Arlaud, G. J., & Frachet, P. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.4.2329 · Cited by 270 · see citing works
Complement-dependent Proinflammatory Properties of the Alzheimer's Disease β-Peptide
Bradt, B. M., Kolb, W. P., & Cooper, N. R. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.3.431 · Cited by 255 · see citing works
The Trem2 R47H variant confers loss-of-function-like phenotypes in Alzheimer's disease
Cheng-Hathaway, P. J., Reed-Geaghan, E. G., Jay, T. R., Casali, B. T., Bemiller, S. M., Puntambekar, S. S., von Saucken, V. E., Williams, R. Y., Karlo, J. C., Moutinho, M., et al. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0262-8 · Cited by 252 · see citing works
Novel allele-dependent role for APOE in controlling the rate of synapse pruning by astrocytes
Chung, W.-S., Verghese, P. B., Chakraborty, C., Joung, J., Hyman, B. T., Ulrich, J. D., Holtzman, D. M., & Barres, B. A. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1609896113 · Cited by 242 · see citing works
Luo, W., Liu, W., Hu, X., Hanna, M., Caravaca, A., & Paul, S. M. (2015) · Scientific Reports · doi:10.1038/srep11161 · Cited by 241 · see citing works
Progranulin protects against amyloid β deposition and toxicity in Alzheimer's disease mouse models
Minami, S. S., Min, S.-W., Krabbe, G., Wang, C., Zhou, Y., Asgarov, R., Li, Y., Martens, L. H., Elia, L. P., Ward, M. E., et al. (2014) · Nature Medicine · doi:10.1038/nm.3672 · Cited by 237 · see citing works
Direct Evidence of Internalization of Tau by Microglia In Vitro and In Vivo
Bolós, M., Llorens-Martín, M., Jurado-Arjona, J., Hernández, F., Rábano, A., & Avila, J. (2016) · Journal of Alzheimer's Disease · doi:10.3233/jad-150704 · Cited by 234 · see citing works
Andreone, B. J., Przybyla, L., Llapashtica, C., Rana, A., Davis, S. S., van Lengerich, B., Lin, K., Shi, J., Mei, Y., Astarita, G., et al. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0650-6 · Cited by 233 · see citing works
Identification of Glycoprotein 330 as an Endocytic Receptor for Apolipoprotein J/Clusterin
Kounnas, M. Z., Loukinova, E. B., Stefansson, S., Harmony, J. A. K., Brewer, B., Strickland, D. K., & Argraves, W. S. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.22.13070 · Cited by 225 · see citing works
MFG-E8 Mediates Primary Phagocytosis of Viable Neurons during Neuroinflammation
Fricker, M., Neher, J. J., Zhao, J.-W., Théry, C., Tolkovsky, A. M., & Brown, G. C. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.4837-11.2012 · Cited by 218 · see citing works
Self-citationJehle, A. W., Gardai, S. J., Li, S., Linsel‐Nitschke, P., Morimoto, K., Janssen, W. J., Vandivier, R. W., Wang, N., Greenberg, S., Dale, B. M., et al. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200601030 · Cited by 213 · see citing works
Cell number changes in Alzheimer's disease relate to dementia, not to plaques and tangles
Andrade-Moraes, C. H., de Oliveira-Pinto, A. V., Castro-Fonseca, E., da Silva, C. G., Guimarães, D. M., Szczupak, D., Parente-Bruno, D. R., Carvalho, L. R. B., Polichiso, L., Valério‐Gomes, B., et al. (2013) · Brain · doi:10.1093/brain/awt273 · Cited by 213 · see citing works
Kanekiyo, T., Zhang, J., Liu, Q., Liu, C.-C., Zhang, L., & Bu, G. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.5491-10.2011 · Cited by 212 · see citing works
Microglial Phagocytosis: A Disease-Associated Process Emerging from Alzheimer’s Disease Genetics
Podleśny-Drabiniok, A., Marcora, E., & Goate, A. M. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.10.002 · Cited by 211 · see citing works
Neniškytė, U., Neher, J. J., & Brown, G. C. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.267583 · Cited by 208 · see citing works
Self-citationWilcock, D. M., Munireddy, S. K., Rosenthal, A., Ugen, K. E., Gordon, M. N., & Morgan, D. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2003.09.015 · Cited by 202 · see citing works
Brelstaff, J., Tolkovsky, A. M., Ghetti, B., Goedert, M., & Spillantini, M. G. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.07.072 · Cited by 195 · see citing works
Alleviation of Neurotoxicity by Microglial Human Siglec-11
Wang, Y., & Neumann, H. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.3940-09.2010 · Cited by 190 · see citing works
Mecca, A. P., O'Dell, R. S., Sharp, E. S., Banks, E. R., Bartlett, H. H., Zhao, W., Lipior, S., Diepenbrock, N. G., Chen, M., Naganawa, M., et al. (2022) · Alzheimer's & Dementia · doi:10.1002/alz.12582 · Cited by 186 · see citing works
Casali, B. T., MacPherson, K. P., Reed-Geaghan, E. G., & Landreth, G. E. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104956 · Cited by 186 · see citing works
Fu, H., Liu, B., Frost, J. L., Hong, S., Jin, M., Ostaszewski, B., Shankar, G. M., Costantino, I. M., Carroll, M. C., Mayadas, T. N., et al. (2012) · Glia · doi:10.1002/glia.22331 · Cited by 180 · see citing works
Dolan, M.-J., Therrien, M., Jereb, S., Kamath, T., Gazestani, V., Atkeson, T., Marsh, S. E., Goeva, A., Lojek, N. M., Murphy, S., et al. (2023) · Nature Immunology · doi:10.1038/s41590-023-01558-2 · Cited by 174 · see citing works
Microglia Elimination Increases Neural Circuit Connectivity and Activity in Adult Mouse Cortex
Liu, Y., Spangenberg, E. E., Tang, B., Holmes, T. C., Green, K. N., & Xu, X. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.2140-20.2020 · Cited by 163 · see citing works
CD33 modulates TREM2: convergence of Alzheimer loci
Chan, G., White, C. C., Winn, P. A., Cimpean, M., Replogle, J. M., Glick, L. R., Cuerdon, N. E., Ryan, K. J., Johnson, K. A., Schneider, J. A., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4126 · Cited by 162 · see citing works
Haure-Mirande, J.-V., Audrain, M., Ehrlich, M. E., & Gandy, S. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00552-w · Cited by 159 · see citing works
Tacnet‐Delorme, P., Chevallier, S., & Arlaud, G. J. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.11.6374 · Cited by 156 · see citing works
Sayed, F. A., Kodama, L., Fan, L., Carling, G. K., Udeochu, J. C., Le, D., Li, Q., Zhou, L., Wong, M. Y., Horowitz, R., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abe3947 · Cited by 155 · cited 3× · see citing works
“For instance, TREM2 R47H can: increase type I interferon response 181,188,192 , increase the response to phosphatidylserine 189,193 and increase microglial phagocytosis of synapses and neurons 189–192 .”
Fricker, M., Oliva-Martín, M. J., & Brown, G. C. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-196 · Cited by 153 · see citing works
Self-citationRushworth, J. V., Jarosz-Griffiths, H., Watt, N. T., & Hooper, N. M. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.400358 · Cited by 151 · see citing works
Sudom, A., Talreja, S., Danao, J., Bragg, E., Kegel, R., Min, X., Richardson, J., Zhang, Z., Sharkov, N., Marcora, E., et al. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.002352 · Cited by 149 · see citing works
Involvement of the Neurotensin Receptor-3 in the Neurotensin-Induced Migration of Human Microglia
Martin, S., Vincent, J., & Mazella, J. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-04-01198.2003 · Cited by 147 · see citing works
Chronic TREM2 activation exacerbates Aβ-associated tau seeding and spreading
Jain, N., Lewis, C. A., Ulrich, J. D., & Holtzman, D. M. (2023) · Journal of Experimental Medicine · doi:10.1084/jem.20220654 · Cited by 146 · see citing works
Microglial mechanisms drive amyloid-β clearance in immunized patients with Alzheimer’s disease
van Olst, L., Simonton, B., Edwards, A. J., Forsyth, A. V., Boles, J. S., Jamshidi, P., Watson, T. H., Shepard, N., Krainc, T., Argue, B. M., et al. (2025) · Nature Medicine · doi:10.1038/s41591-025-03574-1 · Cited by 146 · see citing works
Neher, J. J., Neniškytė, U., Hornik, T. C., & Brown, G. C. (2014) · Glia · doi:10.1002/glia.22693 · Cited by 143 · see citing works
Self-citationAlzheimer's-associated PU.1 expression levels regulate microglial inflammatory response
Pimenova, A. A., Herbinet, M., Gupta, I., Machlovi, S. I., Bowles, K. R., Marcora, E., & Goate, A. M. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105217 · Cited by 141 · see citing works
The endotoxin hypothesis of Alzheimer’s disease
Brown, G. C., & Heneka, M. T. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00722-y · Cited by 140 · see citing works
Self-citationBrelstaff, J. H., Mason, M., Katsinelos, T., McEwan, W. A., Ghetti, B., Tolkovsky, A. M., & Spillantini, M. G. (2021) · Science Advances · doi:10.1126/sciadv.abg4980 · Cited by 135 · see citing works
Acidic pH promotes the formation of toxic fibrils from β-amyloid peptide
Su, Y., & Chang, P.-T. (2001) · Brain Research · doi:10.1016/s0006-8993(00)03322-9 · Cited by 135 · see citing works
Age- and location-related changes in microglial function
Ritzel, R. M., Patel, A. R., Pan, S., Crapser, J., Hammond, M., Jellison, E., & McCullough, L. D. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.02.016 · Cited by 134 · see citing works
Shi, Q., Chang, C., Saliba, A., & Bhat, M. A. (2022) · Journal of Neuroscience · doi:10.1523/jneurosci.2427-21.2022 · Cited by 134 · see citing works
Bartl, M. M., Luckenbach, T., Bergner, O., Ullrich, O., & Koch-Brandt, C. (2001) · Experimental Cell Research · doi:10.1006/excr.2001.5358 · Cited by 132 · see citing works
Cunin, P., Beauvillain, C., Miot, C., Augusto, J., Preisser, L., Blanchard, S., Pignon, P., Scotet, M., Garo, E., Frémaux, I., et al. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.113 · Cited by 132 · see citing works
An exhausted-like microglial population accumulates in aged and APOE4 genotype Alzheimer’s brains
Millet, A., Ledo, J. H., & Tavazoie, S. F. (2024) · Immunity · doi:10.1016/j.immuni.2023.12.001 · Cited by 132 · see citing works
Brown, G. C. (2024) · Nature Reviews Immunology · doi:10.1038/s41577-023-00921-6 · Cited by 129 · see citing works
Self-citationFitz, N. F., Nam, K. N., Wolfe, C. M., Letronne, F., Playso, B. E., Iordanova, B. E., Kozai, T. D. Y., Biedrzycki, R. J., Kagan, V. E., Tyurina, Y. Y., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23762-0 · Cited by 129 · see citing works
Husemann, J., Loike, J. D., Kodama, T., & Silverstein, S. C. (2001) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(01)00239-9 · Cited by 122 · see citing works
Rueda‐Carrasco, J., Sokolova, D., Lee, S., Childs, T., Jurčáková, N., Crowley, G., Schepper, S. D., Ge, J. Z., Lachica, J., Toomey, C. E., et al. (2023) · The EMBO Journal · doi:10.15252/embj.2022113246 · Cited by 120 · see citing works
Puntambekar, S. S., Moutinho, M., Lin, P. B.-C., Jadhav, V., Tumbleson-Brink, D., Balaji, A., Benito, M. A., Xu, G., Oblak, A., Lasagna-Reeves, C. A., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00545-9 · Cited by 113 · see citing works
Nomura, K., Vilalta, A., Allendorf, D. H., Hornik, T. C., & Brown, G. C. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1502532 · Cited by 111 · see citing works
Self-citationThe Phagocytic Code Regulating Phagocytosis of Mammalian Cells
Cockram, T. O. J., Dundee, J. M., Popescu, A. S., & Brown, G. C. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.629979 · Cited by 111 · see citing works
Self-citationMicroglial efferocytosis: Diving into the Alzheimer’s disease gene pool
Romero-Molina, C., Garretti, F., Andrews, S. J., Marcora, E., & Goate, A. M. (2022) · Neuron · doi:10.1016/j.neuron.2022.10.015 · Cited by 111 · cited 1× · see citing works
“Microglial efferocytosis has been proposed to underly much of the genetic risk of AD, based on the genome-wide association study linkage between AD risk and gene variants that affect microglial efferocytosis 86 .”
Tau Oligomer–Containing Synapse Elimination by Microglia and Astrocytes in Alzheimer Disease
Taddei, R. N., Perbet, R., Mate de Gerando, A., Wiedmer, A. E., Sanchez-Mico, M., Connors Stewart, T., Gaona, A., Melloni, A., Amaral, A. C., Duff, K., et al. (2023) · JAMA Neurology · doi:10.1001/jamaneurol.2023.3530 · Cited by 110 · see citing works
Lange, M. L. B., Cenini, G., Piroddi, M., Abdul, H. M., Rukhsana Sultana, A., Galli, F., Memo, M., & Butterfield, D. A. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2007.11.004 · Cited by 110 · see citing works
A cell therapy approach to restore microglial Trem2 function in a mouse model of Alzheimer’s disease
Yoo, Y., Neumayer, G., Shibuya, Y., Mader, M. M.-D., & Wernig, M. (2023) · Cell Stem Cell · doi:10.1016/j.stem.2023.07.006 · Cited by 109 · cited 1× · see citing works
“In future, replacement or reprogramming of defective microglia in AD might be possible 271,272 .”
Cooperation between Engulfment Receptors: The Case of ABCA1 and MEGF10
Hamon, Y., Trompier, D., Ma, Z., Venegas, V., Pophillat, M., Mignotte, V., Zhou, Z., & Chimini, G. (2006) · PLoS ONE · doi:10.1371/journal.pone.0000120 · Cited by 109 · see citing works
Tzioras, M., Daniels, M. J. D., Davies, C., Baxter, P. S., King, D., McKay, S., Varga, B. V., Popovic, K., Hernandez, M., Stevenson, A. J., et al. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101175 · Cited by 109 · see citing works
BIN1 is a key regulator of proinflammatory and neurodegeneration-related activation in microglia
Sudwarts, A., Ramesha, S., Gao, T., Ponnusamy, M., Wang, S., Hansen, M. T., Kozlova, A., Bitarafan, S., Kumar, P., Beaulieu‐Abdelahad, D., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00535-x · Cited by 107 · see citing works
Šimáková, O., & Arispe, N. J. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.3006-07.2007 · Cited by 106 · see citing works
Kaji, S., Berghoff, S. A., Spieth, L., Schlaphoff, L., Sasmita, A. O., Vitale, S., Büschgens, L., Kedia, S., Zirngibl, M., Nazarenko, T., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.09.014 · Cited by 104 · see citing works
Webster, S. D., Galvan, M. D., Ferran, E., Garzon-Rodriguez, W., Glabe, C. G., & Tenner, A. J. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.12.7496 · Cited by 104 · see citing works
ABCA1 influences neuroinflammation and neuronal death
Karasinska, J. M., de Haan, W., Franciosi, S., Ruddle, P., Fan, J., Kruit, J. K., Stukas, S., Lütjohann, D., Gutmann, D. H., Wellington, C. L., et al. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.01.018 · Cited by 104 · see citing works
TREM2 triggers microglial density and age-related neuronal loss
Linnartz‐Gerlach, B., Bodea, L., Klaus, C., Ginolhac, A., Halder, R., Sinkkonen, L., Walter, J., Colonna, M., & Neumann, H. (2019) · Glia · doi:10.1002/glia.23563 · Cited by 104 · see citing works
Blockage of CR1 prevents activation of rodent microglia
Crehan, H., Hardy, J., & Pocock, J. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.02.003 · Cited by 98 · see citing works
ABCA7 Mediates Phagocytic Clearance of Amyloid-β in the Brain
Fu, Y., Hsiao, J.-H. T., Paxinos, G., Halliday, G. M., & Kim, W. S. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160456 · Cited by 98 · see citing works
Jendresen, C., Årskog, V., Daws, M. R., & Nilsson, L. N. G. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0835-4 · Cited by 94 · see citing works
Thomas, A. L., Lehn, M. A., Janssen, E. M., Hildeman, D. A., & Chougnet, C. A. (2022) · Scientific Reports · doi:10.1038/s41598-022-21920-y · Cited by 94 · see citing works
Umpierre, A. D., Li, B., Ayasoufi, K., Simon, W. L., Zhao, S., Xie, M., Thyen, G., Hur, B., Zheng, J., Liang, Y., et al. (2024) · Neuron · doi:10.1016/j.neuron.2024.03.017 · Cited by 94 · see citing works
Rathore, N., Ramani, S. R., Pantua, H., Payandeh, J., Bhangale, T., Wuster, A., Kapoor, M., Sun, Y., Kapadia, S. B., Gonzalez, L., et al. (2018) · PLOS Genetics · doi:10.1371/journal.pgen.1007427 · Cited by 93 · see citing works
Aging and sex: Impact on microglia phagocytosis
Yanguas‐Casás, N., Crespo‐Castrillo, A., Arevalo, M., & Garcia‐Segura, L. M. (2020) · Aging Cell · doi:10.1111/acel.13182 · Cited by 93 · see citing works
Tsai, A. P., Dong, C., Lin, P. B.-C., Messenger, E. J., Casali, B. T., Moutinho, M., Liu, Y., Oblak, A. L., Lamb, B. T., Landreth, G. E., et al. (2022) · Genome Medicine · doi:10.1186/s13073-022-01022-0 · Cited by 92 · see citing works
Anti-inflammatory clearance of amyloid-β by a chimeric Gas6 fusion protein
Jung, H., Lee, S. Y., Lim, S., Choi, H. R., Choi, Y., Kim, M., Kim, S., Lee, Y., Han, K. H., Chung, W., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-01926-9 · Cited by 91 · see citing works
Davis, L. C., Morgan, A. J., & Galione, A. (2020) · The EMBO Journal · doi:10.15252/embj.2019104058 · Cited by 89 · see citing works
Loeffler, D. A. (2023) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-230025 · Cited by 86 · see citing works
Immune checkpoint TIM-3 regulates microglia and Alzheimer’s disease
Kimura, K., Subramanian, A., Yin, Z., Khalilnezhad, A., Wu, Y., He, D., Dixon, K. O., Chitta, U. K., Ding, X., Adhikari, N., et al. (2025) · Nature · doi:10.1038/s41586-025-08852-z · Cited by 85 · see citing works
Vilalta, A., Zhou, Y., Sévalle, J., Griffin, J. K., Satoh, K., Allendorf, D. H., De, S., Puigdellívol, M., Bruzas, A., Burguillos, M. Á., et al. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100631 · Cited by 84 · see citing works
Self-citationInitiative, A. D. N., Takahashi, H., Klein, Z. A., Bhagat, S. M., Kaufman, A. C., Kostylev, M. A., Ikezu, T., & Strittmatter, S. M. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1668-z · Cited by 83 · see citing works
Amyloid-β Oligomers are Sequestered by both Intracellular and Extracellular Chaperones
Narayan, P. S., Meehan, S., Carver, J. A., Wilson, M. R., Dobson, C. M., & Klenerman, D. (2012) · Biochemistry · doi:10.1021/bi301277k · Cited by 82 · see citing works
Sheng, L., Chen, M., Cai, K., Song, Y., Yu, D., Zhang, H., & Xu, G. (2019) · The FASEB Journal · doi:10.1096/fj.201900527r · Cited by 81 · see citing works
Functional insights from biophysical study of TREM2 interactions with apoE and Aβ 1‐42
Kober, D. L., Stuchell‐Brereton, M. D., Kluender, C. E., Dean, H. B., Strickland, M. R., Steinberg, D. F., Nelson, S. S., Baban, B. A., Holtzman, D. M., Frieden, C., et al. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12194 · Cited by 81 · see citing works
Myelination generates aberrant ultrastructure that is resolved by microglia
Djannatian, M., Radha, S., Weikert, U., Safaiyan, S., Wrede, C., Deichsel, C., Kislinger, G., Rhomberg, A., Ruhwedel, T., Campbell, D. S., et al. (2022) · The Journal of Cell Biology · doi:10.1083/jcb.202204010 · Cited by 81 · see citing works
Andersson, C. R., Falsig, J., Stavenhagen, J. B., Christensen, S., Kartberg, F., Rosenqvist, N., Finsen, B. R., & Pedersen, J. T. (2019) · Scientific Reports · doi:10.1038/s41598-019-41105-4 · Cited by 78 · see citing works
Neniškytė, U., & Brown, G. C. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12288 · Cited by 77 · see citing works
Self-citationAllendorf, D. H., Puigdellívol, M., & Brown, G. C. (2019) · Glia · doi:10.1002/glia.23757 · Cited by 76 · see citing works
Self-citationFruhwürth, S., Zetterberg, H., & Paludan, S. R. (2024) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2024.578342 · Cited by 75 · see citing works
The microglial P2Y6 receptor mediates neuronal loss and memory deficits in neurodegeneration
Puigdellívol, M., Milde, S., Vilalta, A., Cockram, T. O. J., Allendorf, D. H., Lee, Y. S., Dundee, J. M., Pampuščenko, K., Borutaitė, V., Nuthall, H. N., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.110148 · Cited by 74 · see citing works
Self-citationAPOE4 confers transcriptomic and functional alterations to primary mouse microglia
Machlovi, S. I., Neuner, S. M., Hemmer, B. M., Khan, R., Liu, Y., Huang, M., Zhu, J. D., Castellano, J. M., Cai, D., Marcora, E., et al. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105615 · Cited by 73 · see citing works
Tsai, A. P., Dong, C., Lin, P. B.-C., Oblak, A. L., Viana Di Prisco, G., Wang, N., Hajicek, N., Carr, A. J., Lendy, E. K., Hahn, O., et al. (2023) · Immunity · doi:10.1016/j.immuni.2023.08.008 · Cited by 71 · see citing works
Liu, T., Zhu, B., Liu, Y., Zhang, X., Yin, J., Li, X., Jiang, L.-L., Hodges, A. P., Rosenthal, S. B., Zhou, L., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20200474 · Cited by 69 · see citing works
Gonzalez-Gil, A., Porell, R. N., Fernandes, S. M., Maenpaa, E., Li, T. A., Li, T., Wong, P. C., Aoki, K., Tiemeyer, M., Yu, Z. J., et al. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.101960 · Cited by 69 · see citing works
Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model
Wu, X., Miller, J. A., Lee, B. T. K., Wang, Y., & Ruedl, C. (2025) · Science Advances · doi:10.1126/sciadv.adq6038 · Cited by 67 · cited 3× · see citing works
“In an amyloid mouse model, plaque-associated microglia were found to accumulate lipid droplets and had reduced phagocytosis compared with microglia not associated with plaques, and the decrease in phagocytosis was reversed by reducing lipid droplet accumulation, resulting in reduced pathology 33 .”
Sialylation acts as a checkpoint for innate immune responses in the central nervous system
Klaus, C., Liao, H., Allendorf, D. H., Brown, G. C., & Neumann, H. (2020) · Glia · doi:10.1002/glia.23945 · Cited by 67 · see citing works
Self-citationThe Importance of Complement-Mediated Immune Signaling in Alzheimer’s Disease Pathogenesis
Batista, A. F., Khan, K., Papavergi, M.-T., & Lemere, C. A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25020817 · Cited by 67 · see citing works
Activation of AMPK by GLP-1R agonists mitigates Alzheimer-related phenotypes in transgenic mice
Zhang, Y., Chen, H., Feng, Y., Liu, M., Lu, Z., Hu, B., Chen, L., Zhang, Y., Liu, J., Cai, F., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00869-3 · Cited by 64 · see citing works
Lv, Z., Chen, L., Chen, P., Peng, H., Rong, Y., Hong, W., Zhou, Q., Li, N., Li, B., Paolicelli, R. C., et al. (2024) · Neuron · doi:10.1016/j.neuron.2023.12.003 · Cited by 63 · see citing works
Self-citationExtracellular tau induces microglial phagocytosis of living neurons in cell cultures
Pampuščenko, K., Morkūnienė, R., Šneideris, T., Smirnovas, V., Budvytytė, R., Valinčius, G., Brown, G. C., & Borutaitė, V. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14940 · Cited by 62 · see citing works
Self-citation(ADNI), A. D. N. I., Kleineidam, L., Chouraki, V., Próchnicki, T., van der Lee, S. J., Madrid-Márquez, L., Wagner-Thelen, H., Karaca, I., Weinhold, L., Wolfsgruber, S., et al. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02138-6 · Cited by 62 · see citing works
Das, R. R., & Chinnathambi, S. (2021) · Traffic · doi:10.1111/tra.12784 · Cited by 62 · see citing works
Bonilla, F. A., Fujita, R. M., Pivniouk, V. I., Chan, A. C., & Geha, R. S. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.040543597 · Cited by 61 · see citing works
Gockley, J., Montgomery, K. S., Poehlman, W. L., Wiley, J. C., Liu, Y., Gerasimov, E. S., Greenwood, A. K., Sieberts, S. K., Wingo, A. P., Wingo, T. S., et al. (2021) · Genome Medicine · doi:10.1186/s13073-021-00890-2 · Cited by 60 · see citing works
Synaptic pruning of murine adult-born neurons by microglia depends on phosphatidylserine
Kurematsu, C., Sawada, M., Ohmuraya, M., Tanaka, M., Kuboyama, K., Ogino, T., Matsumoto, M., Oishi, H., Inada, H., Ishido, Y., et al. (2022) · Journal of Experimental Medicine · doi:10.1084/jem.20202304 · Cited by 60 · see citing works
Chidambaram, H., Das, R. R., & Chinnathambi, S. (2022) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2022.151201 · Cited by 59 · see citing works
Hornik, T. C., Neniškytė, U., & Brown, G. C. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12477 · Cited by 58 · see citing works
Self-citationVelasco, P. T., Heffern, M. C., Sebollela, A. S., Popova, I. A., Lacor, P. N., Lee, K. B., Sun, X., Tiano, B. N., Viola, K. L., Eckermann, A. L., et al. (2012) · ACS Chemical Neuroscience · doi:10.1021/cn300122k · Cited by 55 · see citing works
Lue, L., & Walker, D. G. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10422 · Cited by 55 · see citing works
Gómez-Arboledas, Á., Carvalho, K., Balderrama-Gutierrez, G., Chu, S., Liang, H. Y., Schartz, N. D., Selvan, P., Petrisko, T. J., Pan, M. A., Mortazavi, A., et al. (2022) · Acta Neuropathologica Communications · doi:10.1186/s40478-022-01416-6 · Cited by 55 · see citing works
LILRB2-mediated TREM2 signaling inhibition suppresses microglia functions
Zhao, P., Xu, Y., Jiang, L.-L., Fan, X., Ku, Z., Li, L., Liu, X., Deng, M., Arase, H., Zhu, J.-J., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00550-y · Cited by 54 · see citing works
PICALM Alzheimer’s risk allele causes aberrant lipid droplets in microglia
Kozlova, A., Zhang, S., Sudwarts, A., Zhang, H., Smirnou, S., Byeon, S. K., Thapa, C., Sun, X., Stephenson, K., Zhao, X., et al. (2025) · Nature · doi:10.1038/s41586-025-09486-x · Cited by 53 · see citing works
Karahan, H., Smith, D. C., Kim, B., Dabin, L. C., Al-Amin, M. M., Wijeratne, H. R. S., Pennington, T., Viana di Prisco, G., McCord, B., Lin, P. B.-C., et al. (2021) · Science Advances · doi:10.1126/sciadv.abe3954 · Cited by 53 · cited 1× · see citing works
“Highly expressed in microglia, and knockdown of Abi3 in microglia reduces migration and phagocytosis 226 APP , amyloid-β precursor protein APP acts as a don’t-eat-me signal on neurons 231 .”
Popescu, A. S., Butler, C. A., Allendorf, D. H., Piers, T. M., Mallach, A., Roewe, J., Reinhardt, P., Cinti, A., Redaelli, L., Boudesco, C., et al. (2022) · Glia · doi:10.1002/glia.24318 · Cited by 53 · see citing works
Self-citationHarnessing human iPSC-microglia for CNS-wide delivery of disease-modifying proteins
Chadarevian, J. P., Davtyan, H., Chadarevian, A. L., Nguyen, J., Capocchi, J. K., Le, L., Escobar, A., Chadarevian, T., Mansour, K., Deynega, E., et al. (2025) · Cell stem cell · doi:10.1016/j.stem.2025.03.009 · Cited by 53 · see citing works
Lish, A. M., Grogan, E. F. L., Benoit, C. R., Pearse, R. V., Heuer, S. E., Luquez, T., Orme, G. A., Galle, P. C., Milinkeviciute, G., Green, K. N., et al. (2025) · Neuron · doi:10.1016/j.neuron.2025.03.034 · Cited by 53 · see citing works
Howlett, D. R., Hortobágyi, T., & Francis, P. T. (2013) · Brain Pathology · doi:10.1111/bpa.12057 · Cited by 51 · see citing works
Penney, J., Ralvenius, W. T., Loon, A. R., Cerit, O., Dileep, V., Milo, B., Pao, P., Woolf, H., & Tsai, L. (2023) · Glia · doi:10.1002/glia.24485 · Cited by 51 · see citing works
Chen, Y., Kou, Y., Ni, Y., Yang, H., Xu, C., Fan, H., & Liu, H. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03428-0 · Cited by 51 · see citing works
Tran, K. M., Kawauchi, S., Kramár, E. A., Rezaie, N., Liang, H. Y., Sakr, J., Gómez-Arboledas, Á., Arreola, M. A., da Cunha, C., Phan, J., et al. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00598-4 · Cited by 50 · see citing works
Milde, S., van Tartwijk, F. W., Vilalta, A., Hornik, T. C., Dundee, J. M., Puigdellívol, M., & Brown, G. C. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02280-2 · Cited by 48 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Still being checked.
- Authors
- Brown, G. C., St George-Hyslop, P., Paolicelli, R. C., & Lemke, G.
- Affiliations
- University of Cambridge (GB)
- University of Lausanne (CH)
- Salk Institute for Biological Studies (US)
- Corresponding author
- Brown, Guy C.
- Venue
- Nature Reviews Neurology
- Published
- 2025-11-28
- Volume
- 22
- Issue
- 1
- Pages
- 54-69
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- OpenAlex
- W4416789883
- Semantic Scholar
- 78f3fc40eab69f8c43be0f3bc2dae0bf53ba65f5
- Cited by
- 36
- References
- 273
- Citations by year
- 2026: 36
- FWCI
- 3.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Reviews Neurology (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- Alzheimer's disease, microglial phagocytosis, amyloid plaques, TREM2, anti-amyloid antibodies, synaptic pruning, neurodegeneration, genetic risk factors, complement system, P2Y6 receptor, LRP1, CD33, TAM receptors, tau pathology, disease-modifying therapy
- MeSH terms
- Alzheimer Disease, Animals, Humans, Phagocytosis, Amyloid beta-Peptides, Microglia
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