Microglial phagocytosis in Alzheimer disease

Lecanemab in early Alzheimer's disease

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A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease

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Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages

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Physical basis of cognitive alterations in alzheimer's disease: Synapse loss is the major correlate of cognitive impairment

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Synaptic Pruning by Microglia Is Necessary for Normal Brain Development

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Microglia 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

Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease

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Association 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

Complement and microglia mediate early synapse loss in Alzheimer mouse models

Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., et al. (2016) · Science · doi:10.1126/science.aad8373 · Cited by 3,343 · cited 5×

TREM2 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

The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases

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

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

Alzheimer disease

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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

Complex cell-state changes revealed by single cell RNA sequencing of 76,149 microglia throughout the mouse lifespan and in the injured brain

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

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

TREM2 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

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

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

Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain

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×

Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease

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

Developmental Heterogeneity of Microglia and Brain Myeloid Cells Revealed by Deep Single-Cell RNA Sequencing

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

APOE4 Causes Widespread Molecular and Cellular Alterations Associated with Alzheimer’s Disease Phenotypes in Human iPSC-Derived Brain Cell Types

Lin, 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

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

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 1,012

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

TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia

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

Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer’s disease model

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

Microglial Phagocytosis of Live Neurons

Brown, G. C., & Neher, J. J. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3710 · Cited by 853

Complement activation by beta-amyloid in Alzheimer disease.

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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

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

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

Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation

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

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

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

Brain cell type–specific enhancer–promoter interactome maps and disease - 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 699

Eliminating microglia in Alzheimer’s mice prevents neuronal loss without modulating amyloid-β pathology

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Microglial Cells Internalize Aggregates of the Alzheimer's Disease Amyloid β-Protein Via a Scavenger Receptor

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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

TAM receptors regulate multiple features of microglial physiology

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Biology of the TAM Receptors

Lemke, G. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a009076 · Cited by 598

Apolipoprotein E Is a Ligand for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)

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CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology

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Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease

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ApoE influences amyloid-β (Aβ) clearance despite minimal apoE/Aβ association in physiological conditions

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Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer’s-like pathology

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ABC1 promotes engulfment of apoptotic cells and transbilayer redistribution of phosphatidylserine.

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Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex

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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

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

TREM2 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

Human 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

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×

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

The endotoxin hypothesis of neurodegeneration

Brown, G. C. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1564-7 · Cited by 457

ApoE4 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

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

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 436

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

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

Elevated TREM2 Gene Dosage Reprograms Microglia Responsivity and Ameliorates Pathological Phenotypes in Alzheimer’s Disease Models

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

The biology of TREM receptors

Colonna, M. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-023-00837-1 · Cited by 394

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

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

Complement C3-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

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

Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer’s disease

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

Alzheimer's disease: From immunotherapy to immunoprevention

Jucker, M., & Walker, L. C. (2023) · Cell · doi:10.1016/j.cell.2023.08.021 · Cited by 353

Complement C1q-dependent excitatory and inhibitory synapse elimination by astrocytes and microglia in Alzheimer’s disease mouse models

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

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

Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia

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

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

TREM2 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

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 327

Non-Fc-Mediated Mechanisms Are Involved in Clearance of Amyloid-β In Vivo 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

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

ApoE attenuates unresolvable inflammation by complex formation with activated C1q

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Trem2 restrains the enhancement of tau accumulation and neurodegeneration by β-amyloid pathology

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