TREM2, microglia, and Alzheimer’s disease.

Intraneuronal β-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation

Oakley, H., Cole, S. L., Logan, S., Maus, E., Shao, P., Craft, J., Guillozet-Bongaarts, A., Ohno, M., Disterhoft, J., Van Eldik, L., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1202-06.2006 · Cited by 3,530 · see citing works

Neuropathological alterations in Alzheimer disease

Serrano-Pozo, A., Frosch, M. P., Masliah, E., & Hyman, B. T. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006189 · Cited by 3,345 · see citing works

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 · see citing works

CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer

Stewart, C. R., Stuart, L. M., Wilkinson, K., van Gils, J. M., Deng, J., Halle, A., Rayner, K. J., Boyer, L., Zhong, R., Frazier, W. A., et al. (2010) · Nature Immunology · doi:10.1038/ni.1836 · Cited by 1,513 · see citing works

Disease-Associated Microglia: A Universal Immune Sensor of Neurodegeneration

Deczkowska, A., Keren-Shaul, H., Weiner, A., Colonna, M., Schwartz, M., & Amit, I. (2018) · Cell · doi:10.1016/j.cell.2018.05.003 · Cited by 1,474 · see citing works

Lipid-associated macrophages control metabolic homeostasis in a Trem2-dependent manner

Jaitin, D. A., Adlung, L., Thaiss, C. A., Weiner, A., Li, B., Descamps, H., Lundgren, P., Bleriot, C., Liu, Z., Deczkowska, A., et al. (2019) · Cell · doi:10.1016/j.cell.2019.05.054 · Cited by 1,377 · see citing works

The SYK tyrosine kinase: A crucial player in diverse biological functions

Mócsai, A., Ruland, J., & Tybulewicz, V. L. J. (2010) · Nature Reviews Immunology · doi:10.1038/nri2765 · Cited by 1,368 · see citing works

Microglial Dysfunction and Defective β-Amyloid Clearance Pathways in Aging Alzheimer's Disease Mice

Hickman, S. E., Allison, E. K., & El Khoury, J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.0616-08.2008 · Cited by 1,329 · see citing works

Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes

Bouchon, A., Dietrich, J., & Colonna, M. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.10.4991 · Cited by 1,284 · see citing works

TREM2 Maintains Microglial Metabolic Fitness in Alzheimer’s Disease

Ulland, T. K., Song, W. M., Huang, S. C.-C., Ulrich, J. D., Sergushichev, A., Beatty, W. L., Loboda, A. A., Zhou, Y., Cairns, N. J., Kambal, A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.023 · Cited by 1,263 · see citing works

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 1,126 · see citing works

TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques

Wang, Y., Ulland, T. K., Ulrich, J. D., Song, W., Tzaferis, J. A., Hole, J. T., Yuan, P., Mahan, T. E., Shi, Y., Gilfillan, S., et al. (2016) · Journal of Experimental Medicine · doi:10.1084/jem.20151948 · Cited by 840 · see citing works

TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis

Kleinberger, G., Yamanishi, Y., Suárez-Calvet, M., Czirr, E., Lohmann, E., Cuyvers, E., Struyfs, H., Pettkus, N., Wenninger-Weinzierl, A., Mazaheri, F., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3009093 · Cited by 798 · see citing works

TREM2 regulates microglial cholesterol metabolism upon chronic phagocytic challenge

Nugent, A. A., Lin, K., van Lengerich, B., Lianoglou, S., Przybyla, L., Davis, S. S., Llapashtica, C., Wang, J., Kim, D. J., Xia, D., et al. (2020) · Neuron · doi:10.1016/j.neuron.2019.12.007 · Cited by 745 · see citing works

Scavenger receptor-mediated adhesion of microglia to β-amyloid fibrils

Khoury, J. E., Hickman, S. E., Thomas, C. A., Cao, L., Silverstein, S. C., & Loike, J. D. (1996) · Nature · doi:10.1038/382716a0 · Cited by 727 · see citing works

TREMs in the immune system and beyond

Colonna, M. (2003) · Nature Reviews Immunology · doi:10.1038/nri1106 · Cited by 701 · see citing works

ApoE and Aβ in Alzheimer’s Disease: Accidental Encounters or Partners?

Kanekiyo, T., Xu, H., & Bu, G. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.045 · Cited by 608 · see citing works

CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer's disease

Buerger, K., Ewers, M., Pirttila, T., Zinkowski, R., Alafuzoff, I., Teipel, S. J., DeBernardis, J., Kerkman, D., McCulloch, C., Soininen, H., et al. (2006) · Brain · doi:10.1093/brain/awl269 · Cited by 586 · see citing works

TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy

Leyns, C. E. G., Ulrich, J. D., Finn, M. B., Stewart, F. R., Koscal, L. J., Remolina Serrano, J., Robinson, G. O., Anderson, E., Colonna, M., & Holtzman, D. M. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1710311114 · Cited by 517 · see citing works

New insights into the role of TREM2 in Alzheimer’s disease

Gratuze, M., Leyns, C. E. G., & Holtzman, D. M. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0298-9 · Cited by 489 · see citing works

TREM2-Transduced Myeloid Precursors Mediate Nervous Tissue Debris Clearance and Facilitate Recovery in an Animal Model of Multiple Sclerosis

Takahashi, K., Prinz, M., Stagi, M., Chechneva, O., & Neumann, H. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040124 · Cited by 414 · see citing works

Using Exome Sequencing to Reveal Mutations in TREM2 Presenting as a Frontotemporal Dementia–like Syndrome Without Bone Involvement

Guerreiro, R. J., Lohmann, E., Brás, J. M., Gibbs, J. R., Rohrer, J. D., Gurunlian, N., Dursun, B., Bilgic, B., Hanagasi, H., Gurvit, H., et al. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.579 · Cited by 374 · see citing works

TREM2 deficiency impairs chemotaxis and microglial responses to neuronal injury

Mazaheri, F., Snaidero, N., Kleinberger, G., Madore, C., Daria, A., Werner, G., Krasemann, S., Capell, A., Trümbach, D., Wurst, W., et al. (2017) · The EMBO Reports · doi:10.15252/embr.201743922 · Cited by 351 · see citing works

Heterogeneous expression of the triggering receptor expressed on myeloid cells‐2 on adult murine microglia

Schmid, C. D., Sautkulis, L. N., Danielson, P. E., Cooper, J., Hasel, K. W., Hilbush, B. S., Sutcliffe, J. G., & Carson, M. J. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.01243.x · Cited by 351 · see citing works

Coding variants in TREM2 increase risk for Alzheimer's disease

Jin, S. C., Benitez, B. A., Karch, C. M., Cooper, B., Skorupa, T., Carrell, D., Norton, J. B., Hsu, S., Harari, O., Cai, Y., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu277 · Cited by 314 · see citing works

The Triggering Receptor Expressed on Myeloid Cells 2 Binds Apolipoprotein E

Bailey, C. C., DeVaux, L. B., & Farzan, M. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.677286 · Cited by 303 · see citing works

Altered microglial response to Aβ plaques in APPPS1-21 mice heterozygous for TREM2

Ulrich, J. D., Finn, M. B., Wang, Y., Shen, A., Mahan, T. E., Jiang, H., Stewart, F. R., Piccio, L., Colonna, M., & Holtzman, D. M. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-20 · Cited by 302 · see citing works

Alzheimer's disease‐associated TREM2 variants exhibit either decreased or increased ligand‐dependent activation

Song, W., Hooli, B., Mullin, K., Jin, S. C., Cella, M., Ulland, T. K., Wang, Y., Tanzi, R. E., & Colonna, M. (2017) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.07.004 · Cited by 297 · see citing works

Pattern Recognition by TREM-2: Binding of Anionic Ligands

Daws, M. R., Sullam, P. M., Niemi, E. C., Chen, T. T., Tchao, N. K., & Seaman, W. E. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.2.594 · Cited by 291 · see citing works

Blockade of TREM‐2 exacerbates experimental autoimmune encephalomyelitis

Piccio, L., Buonsanti, C., Mariani, M., Cella, M., Gilfillan, S., Cross, A. H., Colonna, M., & Panina‐Bordignon, P. (2007) · European Journal of Immunology · doi:10.1002/eji.200636837 · Cited by 284 · see citing works

Microglial internalization and degradation of pathological tau is enhanced by an anti-tau monoclonal antibody

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

Microglia contributes to plaque growth by cell death due to uptake of amyloid β in the brain of Alzheimer's disease mouse model: Aβ Plaque Formation and Microglial Activation

Baik, S. H., Kang, S., Son, S. M., & Mook-Jung, I. (2016) · Glia · doi:10.1002/glia.23074 · Cited by 234 · see citing works

Differential effects of partial and complete loss of TREM2 on microglial injury response and tauopathy

Sayed, F. A., Telpoukhovskaia, M., Kodama, L., Li, Y., Zhou, Y., Le, D., Hauduc, A., Ludwig, C., Gao, F., Clelland, C., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1811411115 · Cited by 229 · see citing works

TREM2 and the neuroimmunology of Alzheimer's disease

Hickman, S. E., & El Khoury, J. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.11.021 · Cited by 221 · see citing works

TREM-2 promotes macrophage survival and lung disease after respiratory viral infection

Wu, K., Byers, D. E., Jin, X., Agapov, E., Alexander-Brett, J., Patel, A. C., Cella, M., Gilfilan, S., Colonna, M., Kober, D. L., et al. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20141732 · Cited by 207 · see citing works

TREM2 modifies microglial phenotype and provides neuroprotection in P301S tau transgenic mice

Jiang, T., Zhang, Y.-D., Chen, Q., Gao, Q., Zhu, X.-C., Zhou, J.-S., Shi, J.-Q., Lu, H., Tan, L., & Yu, J.-T. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.01.028 · Cited by 176 · see citing works

Mechanisms of microglia accumulation in Alzheimer’s disease: therapeutic implications

Khoury, J. E., & Luster, A. D. (2008) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2008.08.004 · Cited by 171 · see citing works

TREM2 is associated with the risk of Alzheimer's disease in Spanish population

Benitez, B. A., Cooper, B., Pastor, P., Jin, S.-C., Lorenzo, E., Cervantes, S., & Cruchaga, C. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.12.018 · Cited by 163 · see citing works

Human Induced Pluripotent Stem Cell-Derived Microglia-Like Cells Harboring TREM2 Missense Mutations Show Specific Deficits in Phagocytosis

Garcia-Reitboeck, P., Phillips, A., Piers, T. M., Villegas-Llerena, C., Butler, M., Mallach, A., Rodrigues, C., Arber, C. E., Heslegrave, A., Zetterberg, H., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.07.094 · Cited by 162 · see citing works

<scp>TREM</scp>2 Protein Expression Changes Correlate with <scp>A</scp>lzheimer's Disease Neurodegenerative Pathologies in Post‐Mortem Temporal Cortices

Lue, L., Schmitz, C. T., Serrano, G., Sue, L. I., Beach, T. G., & Walker, D. G. (2015) · Brain Pathology · doi:10.1111/bpa.12190 · Cited by 154 · see citing works

TREM2 is associated with increased risk for Alzheimer’s disease in African Americans

Jin, S. C., Carrasquillo, M. M., Benitez, B. A., Skorupa, T., Carrell, D., Patel, D., Lincoln, S., Krishnan, S., Kachadoorian, M., Reitz, C., et al. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0016-9 · Cited by 153 · see citing works

<i>R47H TREM2</i> variant increases risk of typical early‐onset Alzheimer's disease but not of prion or frontotemporal dementia

Slattery, C. F., Beck, J. A., Harper, L., Adamson, G., Abdi, Z., Uphill, J., Campbell, T., Druyeh, R., Mahoney, C. J., Rohrer, J. D., et al. (2014) · Alzheimer's &amp; Dementia · doi:10.1016/j.jalz.2014.05.1751 · Cited by 119 · see citing works

Silencing of TREM2 exacerbates tau pathology, neurodegenerative changes, and spatial learning deficits in P301S tau transgenic mice

Jiang, T., Tan, L., Zhu, X.-C., Zhou, J.-S., Cao, L., Tan, M.-S., Wang, H.-F., Chen, Q., Zhang, Y.-D., & Yu, J.-T. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.08.019 · Cited by 111 · see citing works

A rare coding variant in TREM2 increases risk for Alzheimer's disease in Han Chinese

Jiang, T., Tan, L., Chen, Q., Tan, M.-S., Zhou, J.-S., Zhu, X.-C., Lu, H., Wang, H.-F., Zhang, Y.-D., & Yu, J.-T. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.02.023 · Cited by 110 · see citing works

Rare TREM2 variants associated with Alzheimer’s disease display reduced cell surface expression

Sirkis, D. W., Bonham, L. W., Aparicio, R. E., Geier, E. G., Ramos, E. M., Wang, Q., Karydas, A., Miller, Z. A., Miller, B. L., Coppola, G., et al. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0367-7 · Cited by 61 · see citing works

A candidate regulatory variant at the <i>TREM</i> gene cluster associates with decreased Alzheimer's disease risk and increased <i>TREML1</i> and <i>TREM2</i> brain gene expression

Carrasquillo, M. M., Allen, M., Burgess, J. D., Wang, X., Strickland, S. L., Aryal, S., Siuda, J., Kachadoorian, M. L., Medway, C., Younkin, C. S., et al. (2017) · Alzheimer's &amp; Dementia · doi:10.1016/j.jalz.2016.10.005 · Cited by 58 · see citing works

Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies.

Zhang, J., Zhang, Y., Wang, J., Xia, Y., Zhang, J., & Chen, L. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01911-3 · Cited by 1,138 · see citing works

TREM2 in the pathogenesis of AD: a lipid metabolism regulator and potential metabolic therapeutic target

Li, R.-Y., Qin, Q., Yang, H.-C., Wang, Y.-Y., Mi, Y.-X., Yin, Y.-S., Wang, M., Yu, C.-J., & Tang, Y. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00542-y · Cited by 204 · see citing works

Brain cell type-specific cholesterol metabolism and implications for learning and memory

Li, D., Zhang, J., & Liu, Q. (2022) · Trends in Neurosciences · doi:10.1016/j.tins.2022.01.002 · Cited by 163 · see citing works

Glycometabolic Reprogramming of Microglia in Neurodegenerative Diseases: Insights from Neuroinflammation

Huang, Q., Wang, Y., Chen, S., & Liang, F. (2023) · Aging and disease · doi:10.14336/ad.2023.0807 · Cited by 62 · see citing works

Symptomatic and Disease-Modifying Therapy Pipeline for Alzheimer’s Disease: Towards a Personalized Polypharmacology Patient-Centered Approach

Morató, X., Pytel, V., Jofresa, S., Ruiz, A., & Boada, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23169305 · Cited by 53 · see citing works

The role of TREM2 in Alzheimer’s disease: from the perspective of Tau

Huang, W., Huang, J., Huang, N., & Luo, Y. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1280257 · Cited by 49 · see citing works

COVID-19 as a Risk Factor for Alzheimer’s Disease

Golzari-Sorkheh, M., Weaver, D. F., & Reed, M. A. (2023) · Journal of Alzheimer's Disease · doi:10.3233/jad-220800 · Cited by 39 · see citing works

Integrative single-nucleus multi-omics analysis prioritizes candidate cis and trans regulatory networks and their target genes in Alzheimer’s disease brains

Gamache, J., Gingerich, D., Shwab, E. K., Barrera, J., Garrett, M. E., Hume, C., Crawford, G. E., Ashley-Koch, A. E., & Chiba-Falek, O. (2023) · Cell &amp; Bioscience · doi:10.1186/s13578-023-01120-5 · Cited by 20 · see citing works

Molecular mechanisms of Alzheimer’s disease: From therapeutic targets to promising drugs

Alan, E., Kerry, Z., & Sevin, G. (2023) · Fundamental &amp; Clinical Pharmacology · doi:10.1111/fcp.12861 · Cited by 17 · see citing works

TREM2 and microglial immunity in Alzheimer’s disease: mechanisms, genetics, and therapeutic opportunities

Wang, T., Liu, X., Wang, X., Hua, F., & Yan, L. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1739875 · Cited by 14 · see citing works

PU.1 dictates β-amyloid-induced TREM2 expression upregulation in microglia in a transgenic model of Alzheimer’s disease

Wei, Z., Pan, X., Cui, X., Zhang, J., Dai, X., Zeng, Y., & Chen, X. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1537388 · Cited by 7 · see citing works