The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
Alzheimer's disease‐associated TREM2 variants exhibit either decreased or increased ligand‐dependent activation
Open accessAbstract
Introduction: TREM2 is a lipid‐sensing activating receptor on microglia known to be important for Alzheimer's disease (AD), but whether it plays a beneficial or detrimental role in disease pathogenesis is controversial. Methods: We analyzed AD risk of TREM2 variants in the NIMH AD Genetics Initiative Study and AD Sequencing Project. We compared each variant's risk and functional impact by a reporter assay. Finally, we analyzed expression of TREM2 on human monocytes. Results: We provide more evidence for increased AD risk associated with several TREM2 variants, and show that these variants decreased or markedly increased binding to TREM2 ligands. We identify HDL and LDL as novel TREM2 ligands. We also show that TREM2 expression in human monocytes is minimal compared to monocyte‐derived dendritic cells. Discussion: Our results suggest that TREM2 signaling helps protect against AD but can cause harm in excess, supporting the idea that proper TREM2 function is important to counteract disease progression.
Overview
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
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The most characterised variant of TREM2 (p.R47H) shows defects in ligand binding [6, 37, 38, 97], which impacts the ability of TREM2 to recognise damage, and induce microglial changes, resulting in a dampened response to pathological insults such as Aβ deposition.”
From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [97]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“such as reduced ligand binding (p.R47H [96], p.R62H [97])”
From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [97]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“A number of mutations in PLCG2 (about 75%), that have been previously implicated in various inflammatory diseases [92–102], actually map to the autoinhibitory interface on the PLCγ2 model structure and can be considered as pathogenic (Fig. 2c)”
From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [97]
Experimental — accuracy not yet measuredIn the citing paper
“TREM2 binds polyanions, particularly phospholipids and sulfatides that may be exposed in the brain during Aβ accumulation due to neuronal cell apoptosis and myelin damage (114).”
From Microglia Function in the Central Nervous System During Health and Neurodegeneration (2017) · cites this paper as [115]
In the citing paper
“In the initial week following injury, the microglia population adopts a balanced distribution between pro- and anti-inflammatory states to promote neurogenesis and enhance the immune response to injury [89,110,111].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [89]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G. S., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.5.1977 · Cited by 4,268
Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.440 · Cited by 3,326
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
Variant of TREM2 Associated with the Risk of Alzheimer's Disease
Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211103 · Cited by 2,558
Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease
the European Alzheimer's Disease Initiative Investigators, Lambert, J.-C., Heath, S., Even, G., Campion, D., Sleegers, K., Hiltunen, M., Combarros, O., Zelenika, D., Bullido, M. J., et al. (2009) · Nature Genetics · doi:10.1038/ng.439 · Cited by 2,234
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
Self-citationInnate immunity in Alzheimer's disease
Heneka, M. T., Golenbock, D. T., & Latz, E. (2015) · Nature Immunology · doi:10.1038/ni.3102 · Cited by 902
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
Self-citationJay, T. R., Miller, C. M., Cheng, P. J., Graham, L. C., Bemiller, S., Broihier, M. L., Xu, G., Margevicius, D., Karlo, J. C., Sousa, G. L., et al. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20142322 · Cited by 682 · cited 1×
“However, mixed results were reported with regard to plaque burden [7,8], and therefore, as with microglia in general, it is not settled whether TREM2 plays a beneficial or detrimental role in the context of AD.”
ResultApolipoprotein 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
Cited by
Sorted by citations
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
Self-citationMicroglia Function in the Central Nervous System During Health and Neurodegeneration
Colonna, M., & Butovsky, O. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-051116-052358 · Cited by 2,894
Self-citationMicroglia in Alzheimer’s disease
Hansen, D. V., Hanson, J. E., & Sheng, M. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201709069 · Cited by 1,935
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
Self-citationVan Hove, H., Martens, L., Scheyltjens, I., De Vlaminck, K., Pombo Antunes, A. R., De Prijck, S., Vandamme, N., De Schepper, S., Van Isterdael, G., Scott, C. L., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0393-4 · Cited by 1,074
TREM2 — a key player in microglial biology and Alzheimer disease
Ulland, T. K., & Colonna, M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0072-1 · Cited by 735
Self-citationTREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy
Molgora, M., Esaulova, E., Vermi, W., Hou, J., Chen, Y., Luo, J., Brioschi, S., Bugatti, M., Omodei, A. S., Ricci, B., et al. (2020) · Cell · doi:10.1016/j.cell.2020.07.013 · Cited by 656
Self-citationAlzheimer’s disease hypothesis and related therapies
Du, X., Wang, X., & Geng, M. (2018) · Translational Neurodegeneration · doi:10.1186/s40035-018-0107-y · Cited by 623
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
Self-citationAstrocytic and microglial cells as the modulators of neuroinflammation in Alzheimer’s disease
Singh, D. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02565-0 · Cited by 569
Wang, S., Mustafa, M., Yuede, C. M., Salazar, S. V., Kong, P., Long, H., Ward, M., Siddiqui, O., Paul, R., Gilfillan, S., et al. (2020) · Journal of Experimental Medicine · doi:10.1084/jem.20200785 · Cited by 549
Self-citationLeyns, 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
Self-citationNew 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
TREM2, microglia, and neurodegenerative diseases
Yeh, F. L., Hansen, D. V., & Sheng, M. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.03.008 · Cited by 440
Alzheimer’s disease: insights into pathology, molecular mechanisms, and therapy
Zheng, Q., & Wang, X. (2024) · Protein & Cell · doi:10.1093/procel/pwae026 · Cited by 483
TREM2 in Neurodegenerative Diseases
Jay, T. R., von Saucken, V. E., & Landreth, G. E. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0197-5 · Cited by 427
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
Self-citationColonna, M. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-023-00837-1 · Cited by 394
Self-citationMcQuade, A., Kang, Y. J., Hasselmann, J., Jairaman, A., Sotelo, A., Coburn, M., Shabestari, S. K., Chadarevian, J. P., Fote, G., Tu, C. H., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19227-5 · Cited by 361
Immune Signaling in Neurodegeneration
Hammond, T. R., Marsh, S. E., & Stevens, B. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.016 · Cited by 336
Elucidating the Role of TREM2 in Alzheimer’s Disease
Ulrich, J. D., Ulland, T. K., Colonna, M., & Holtzman, D. M. (2017) · Neuron · doi:10.1016/j.neuron.2017.02.042 · Cited by 325
Self-citationThe identity and function of microglia in neurodegeneration
Song, W. M., & Colonna, M. (2018) · Nature Immunology · doi:10.1038/s41590-018-0212-1 · Cited by 308
Self-citationHumanized 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
Self-citationApoE facilitates the microglial response to amyloid plaque pathology
Ulrich, J. D., Ulland, T. K., Mahan, T. E., Nyström, S., Nilsson, K. P., Song, W. M., Zhou, Y., Reinartz, M., Choi, S., Jiang, H., et al. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20171265 · Cited by 297
Self-citationMicroglia in Alzheimer’s disease: pathogenesis, mechanisms, and therapeutic potentials
Miao, J., Ma, H., Yang, Y., Liao, Y., Lin, C., Zheng, J., Yu, M., & Lan, J. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1201982 · Cited by 293
TREM2-Ligand Interactions in Health and Disease
Kober, D. L., & Brett, T. J. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.04.004 · Cited by 284
Schlepckow, K., Kleinberger, G., Fukumori, A., Feederle, R., Lichtenthaler, S. F., Steiner, H., & Haass, C. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201707672 · Cited by 266
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
Impact of TREM2R47H variant on tau pathology–induced gliosis and neurodegeneration
Gratuze, M., Leyns, C. E. G., Sauerbeck, A. D., St-Pierre, M.-K., Xiong, M., Kim, N., Serrano, J. R., Tremblay, M.-È., Kummer, T. T., Colonna, M., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci138179 · Cited by 252
Self-citationThe role of TREM2 in Alzheimer's disease and other neurodegenerative disorders
Carmona, S., Zahs, K., Wu, E., Dakin, K., Bras, J., & Guerreiro, R. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30232-1 · Cited by 244
van Lengerich, B., Zhan, L., Xia, D., Chan, D., Joy, D., Park, J. I., Tatarakis, D., Calvert, M., Hummel, S., Lianoglou, S., et al. (2023) · Nature Neuroscience · doi:10.1038/s41593-022-01240-0 · Cited by 233
Jurcău, M. C., Andronie-Cioara, F. L., Jurcău, A., Marcu, F., Ţiț, D. M., Pașcalău, N., & Nistor-Cseppentö, D. C. (2022) · Antioxidants · doi:10.3390/antiox11112167 · Cited by 226
Endo-lysosomal dysregulations and late-onset Alzheimer’s disease: impact of genetic risk factors
Van Acker, Z. P., Bretou, M., & Annaert, W. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0323-7 · Cited by 222
Emerging Microglia Biology Defines Novel Therapeutic Approaches for Alzheimer’s Disease
Lewcock, J. W., Schlepckow, K., Di Paolo, G., Tahirovic, S., Monroe, K. M., & Haass, C. (2020) · Neuron · doi:10.1016/j.neuron.2020.09.029 · Cited by 221
TREM2, microglia, and Alzheimer’s disease.
Qin, Q., Teng, Z., Liu, C., Li, Q., Yin, Y., & Tang, Y. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111438 · Cited by 219
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
Self-citationAdvancing cell therapy for neurodegenerative diseases
Temple, S. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.03.017 · Cited by 221
Wang, Y., Lin, Y., Wang, L., Zhan, H., Luo, X., Zeng, Y., Wu, W., Zhang, X., & Wang, F. (2020) · Aging · doi:10.18632/aging.104104 · Cited by 196
Self-citationThe role of innate immune genes in Alzheimer's disease
Griciuc, A., & Tanzi, R. E. (2021) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000911 · Cited by 192
Self-citationAlzheimer’s Disease, Oligomers, and Inflammation
Forloni, G., & Balducci, C. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170819 · Cited by 205
TREM2 dependent and independent functions of microglia in Alzheimer’s disease
Hou, J., Chen, Y., Grajales-Reyes, G., & Colonna, M. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00588-y · Cited by 191
Self-citationFeuerbach, D., Schindler, P. A., Barske, C., Joller, S., Beng-Louka, E., Worringer, K. A., Kommineni, S., Kaykas, A., Ho, D. J., Ye, C., et al. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.09.034 · Cited by 179
Molecular Mechanisms of Neuroinflammation in Aging and Alzheimer’s Disease Progression
Andronie-Cioară, F. L., Ardelean, A. I., Nistor-Cseppento, C. D., Jurcău, A., Jurcău, M. C., Pașcalău, N., & Marcu, F. M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24031869 · Cited by 170
High‐affinity interactions and signal transduction between Aβ oligomers and TREM2
Lessard, C. B., Malnik, S. L., Zhou, Y., Ladd, T. B., Cruz, P. E., Ran, Y., Chakrabaty, P., Mahan, T. E., Holtzman, D. M., Ulrich, J. D., et al. (2018) · EMBO Molecular Medicine · doi:10.15252/emmm.201809027 · Cited by 156
Self-citationZhao, P., Xu, Y., Jiang, L., Fan, X., Li, L., Li, X., Arase, H., Zhao, Y., Cao, W., Zheng, H., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abq0095 · Cited by 141
Soluble TREM2: Innocent bystander or active player in neurological diseases?
Filipello, F., Goldsbury, C., You, S. F., Locca, A., Karch, C. M., & Piccio, L. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105630 · Cited by 134
Cheng, Q., Danao, J., Talreja, S., Wen, P. H., Yin, J., Sun, N., Li, C.-M., Chui, D., Tran, D. T., Koirala, S., et al. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.001848 · Cited by 129
Fitz, 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
Transgenic Mouse Models of Alzheimer’s Disease: An Integrative Analysis
Sanchez-Varo, R. M., Mejias‐Ortega, M., Fernandez-Valenzuela, J. J., Nuñez‐Diaz, C., Cáceres-Palomo, L., Vegas‐Gomez, L., Sánchez‐Mejías, E., Trujillo‐Estrada, L., García‐León, J. A., Moreno‐González, I., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105404 · Cited by 136
Teter, B., Morihara, T., Lim, G. P., Chu, T., Jones, M. R., Zuo, X., Paul, R. M., Frautschy, S. A., & Cole, G. M. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.02.015 · Cited by 127
Potential Bidirectional Relationship Between Periodontitis and Alzheimer’s Disease
Liccardo, D., Marzano, F., Carraturo, F., Guida, M., Femminella, G. D., Bencivenga, L., Agrimi, J., Addonizio, A., Melino, I., Valletta, A., et al. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00683 · Cited by 148
Prokop, S., Miller, K. R., Labra, S. R., Pitkin, R. M., Hoxha, K., Narasimhan, S., Changolkar, L., Rosenbloom, A., Lee, V. M.-Y., & Trojanowski, J. Q. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02048-2 · Cited by 119
Aminophospholipids are signal-transducing TREM2 ligands on apoptotic cells
Shirotani, K., Hori, Y., Yoshizaki, R., Higuchi, E., Colonna, M., Saito, T., Hashimoto, S., Saito, T., Saido, T. C., & Iwata, N. (2019) · Scientific Reports · doi:10.1038/s41598-019-43535-6 · Cited by 116
Self-citationTREM2-independent microgliosis promotes tau-mediated neurodegeneration in the presence of ApoE4.
Gratuze, M., Schlachetzki, J. C. M., D’Oliveira Albanus, R., Jain, N., Novotny, B., Brase, L., Rodriguez, L., Mansel, C., Kipnis, M., O’Brien, S., et al. (2023) · Neuron · doi:10.1016/j.neuron.2022.10.022 · Cited by 115
Self-citationTREM2 ectodomain and its soluble form in Alzheimer’s disease
Yang, J., Fu, Z., Zhang, X., Xiong, M., Meng, L., & Zhang, Z. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01878-2 · Cited by 113
Elevating microglia TREM2 reduces amyloid seeding and suppresses disease-associated microglia
Zhao, N., Qiao, W., Li, F., Ren, Y., Zheng, J., Martens, Y. A., Wang, X., Li, L., Liu, C., Chen, K., et al. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20212479 · Cited by 116
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
Distinct Signaling Pathways Regulate TREM2 Phagocytic and NFκB Antagonistic Activities
Yao, H., Coppola, K., Schweig, J. E., Crawford, F., Mullan, M., & Paris, D. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00457 · Cited by 110
Microglia in Alzheimer’s disease: A target for immunotherapy
Wang, S., & Colonna, M. (2019) · Journal of Leukocyte Biology · doi:10.1002/jlb.mr0818-319r · Cited by 106
Self-citationSingle-nucleus RNA-sequencing of autosomal dominant Alzheimer disease and risk variant carriers
Brase, L., You, S., Albanus, R. D., Del‐Aguila, J. L., Dai, Y., Novotny, B. C., Soriano‐Tárraga, C., Dykstra, T., Fernández, M. V., Budde, J., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37437-5 · Cited by 104
Cellular Receptors of Amyloid β Oligomers (AβOs) in Alzheimer’s Disease
Mroczko, B., Groblewska, M., Litman-Zawadzka, A., Kornhuber, J., & Lewczuk, P. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19071884 · Cited by 97
Spatially restricted and ontogenically distinct hepatic macrophages are required for tissue repair
De Ponti, F. F., Bujko, A., Liu, Z., Collins, P. J., Schuermans, S., Maueroder, C., Amstelveen, S., Thoné, T., Martens, L., McKendrick, J. G., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.01.002 · Cited by 94
Effect of high fat diet on phenotype, brain transcriptome and lipidome in Alzheimer’s model mice
Nam, K. N., Mounier, A., Wolfe, C. M., Fitz, N. F., Carter, A. Y., Castranio, E. L., Kamboh, H., Reeves, V. L., Wang, J., Han, X., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-04412-2 · Cited by 96
TREM2 in Alzheimer’s Disease: Microglial Survival and Energy Metabolism
Zheng, H., Cheng, B., Li, Y., Li, X., Chen, X., & Zhang, Y.-W. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00395 · Cited by 94
Metabolic Dysfunction in Alzheimer’s Disease: From Basic Neurobiology to Clinical Approaches
Clarke, J. R., Ribeiro, F. C., Frozza, R. L., Felice, F. G. D., & Lourenco, M. V. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-179911 · Cited by 93
TREM2‐dependent effects on microglia in Alzheimer's disease
Zhou, Y., Ulland, T. K., & Colonna, M. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00202 · Cited by 82
Self-citationMicroglia heterogeneity along a spatio–temporal axis: More questions than answers
Silvin, A., & Ginhoux, F. (2018) · Glia · doi:10.1002/glia.23458 · Cited by 90
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
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 82
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 86
Acute Trem2 reduction triggers increased microglial phagocytosis, slowing amyloid deposition in mice
Schoch, K. M., Ezerskiy, L. A., Morhaus, M. M., Bannon, R. N., Sauerbeck, A. D., Shabsovich, M., Jafar-nejad, P., Rigo, F., & Miller, T. M. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2100356118 · Cited by 78
TREM2 regulates innate immunity in Alzheimer’s disease
Li, J.-T., & Zhang, Y. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1148-y · Cited by 76
Neuroinflammatory Signaling in the Pathogenesis of Alzheimer’s Disease
Uddin, M. S., Kabir, M. T., Jalouli, M., Rahman, M. A., Jeandet, P., Behl, T., Alexiou, A. T., Albadrani, G. M., Abdel‐Daim, M. M., Perveen, A., et al. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666210826130210 · Cited by 76
Current views on meningeal lymphatics and immunity in aging and Alzheimer’s disease
Rego, S., Sánchez, G., & Mesquita, S. D. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00645-0 · Cited by 79
TREM2 and sTREM2 in Alzheimer’s disease: from mechanisms to therapies
Zhang, L., Xiang, X., Li, Y., Bu, G., & Chen, X. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00834-z · Cited by 87
Li, J., Sun, M., Cui, X., & Li, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231710020 · Cited by 71
Untangling senescent and damage‐associated microglia in the aging and diseased brain
Ng, P. Y., McNeely, T. L., & Baker, D. J. (2023) · The FEBS Journal · doi:10.1111/febs.16315 · Cited by 68
Gupta, N., Shyamasundar, S., Patnala, R., Karthikeyan, A., Arumugam, T. V., Ling, E., & Dheen, S. T. (2018) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2018.1515917 · Cited by 67
Reassessment of Pioglitazone for Alzheimer’s Disease
Saunders, A. M., Burns, D. K., & Gottschalk, W. K. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.666958 · Cited by 71
Magno, L., Bunney, T. D., Mead, E., Svensson, F., & Bictash, M. N. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00436-5 · Cited by 64
The Amyloid-Beta Clearance: From Molecular Targets to Glial and Neural Cells
Cai, W., Wu, T., & Chen, N. (2023) · Biomolecules · doi:10.3390/biom13020313 · Cited by 69
Novel targets in Alzheimer’s disease: A special focus on microglia
Balducci, C., & Forloni, G. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.01.017 · Cited by 62
Secretases in Alzheimer's disease: Novel insights into proteolysis of APP and TREM2
Lichtenthaler, S. F., Tschirner, S. K., & Steiner, H. (2022) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2021.09.003 · Cited by 60
Impact of aging immune system on neurodegeneration and potential immunotherapies
Liang, Z., Zhao, Y., Ruan, L., Zhu, L., Jin, K., Zhuge, Q., Su, D., & Zhao, Y. L. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.07.006 · Cited by 64
Microglial Immunometabolism in Alzheimer’s Disease
Shippy, D. C., & Ulland, T. K. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.563446 · Cited by 56
Self-citationLILRB2-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
Role of TREM2 in Alzheimer’s Disease: A Long Road Ahead
Kulkarni, B., Kumar, D., Martins, N. A., & Sellamuthu, S. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02477-9 · Cited by 53
Microglial activation as a hallmark of neuroinflammation in Alzheimer’s disease
Ebrahimi, R., Nejad, S. S., Tafti, M. F., Karimi, Z., Sadr, S. R., Hussein, D. R., Talebian, N., & Esmaeilpour, K. (2025) · Metabolic Brain Disease · doi:10.1007/s11011-025-01631-9 · Cited by 58
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 57
Martín‐Sánchez, A., Piñero, J., Nonell, L., Arnal, M., Ribé, E. M., Nevado‐Holgado, A. J., Lovestone, S., Sanz, F., Furlong, L. I., & Valverde, O. (2021) · Alzheimer s Research & Therapy · doi:10.1186/s13195-021-00810-x · Cited by 52
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 55
Tipping points in neurodegeneration
Simons, M., Levin, J., & Dichgans, M. (2023) · Neuron · doi:10.1016/j.neuron.2023.05.031 · Cited by 52
Zhao, Z., Liu, Y., Ruan, S., & Hu, Y. (2023) · International Journal of Nanomedicine · doi:10.2147/ijn.s444115 · Cited by 49
Deming, Y. K., Li, Z., Benítez, B. A., & Cruchaga, C. (2018) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2018.1486823 · Cited by 51
Penney, J., Ralvenius, W. T., Loon, A., Cerit, O., Dileep, V., Milo, B., Pao, P., Woolf, H., & Tsai, L. (2024) · Glia · doi:10.1002/glia.24485 · Cited by 52
Chemicals used for the induction of Alzheimer’s disease-like cognitive dysfunctions in rodents
Mahdi, O., Baharuldin, M. T. H., Nor, N. H. M., Chiroma, S. M., Jagadeesan, S., & Moklas, M. A. M. (2019) · Biomedical Research and Therapy · doi:10.15419/bmrat.v6i11.575 · Cited by 53
Overview of therapeutic targets in management of dementia
Malik, R., Kalra, S., Bhatia, S., Al‐Harrasi, A., Singh, G., Mohan, S., Makeen, H. A., Albratty, M., Meraya, A. M., Bahar, B., et al. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113168 · Cited by 51
TREM2 splice isoforms generate soluble TREM2 species that disrupt long-term potentiation
Moutinho, M., Coronel, I., Tsai, A. P., Di Prisco, G. V., Pennington, T., Atwood, B. K., Puntambekar, S. S., Smith, D. C., Martinez, P., Han, S., et al. (2023) · Genome Medicine · doi:10.1186/s13073-023-01160-z · Cited by 42
TREM-2 is a sensor and activator of T cell response in SARS-CoV-2 infection
Wu, Y., Wang, M., Yin, H., Ming, S., Li, X., Jiang, G., Liu, Y., Wang, P., Zhou, G., Liu, L., et al. (2021) · Science Advances · doi:10.1126/sciadv.abi6802 · Cited by 45
Plasma levels of soluble TREM2 and neurofilament light chain in TREM2 rare variant carriers
Ashton, N. J., Suárez‐Calvet, M., Heslegrave, A., Hye, A., Razquín, C., Pástor, P., Sánchez‐Valle, R., Molinuevo, J. L., Visser, P. J., Blennow, K., et al. (2019) · Alzheimer s Research & Therapy · doi:10.1186/s13195-019-0545-5 · Cited by 45
Metadata
- Authors
- Song, W., Hooli, B., Mullin, K., Jin, S. C., Cella, M., Ulland, T. K., Wang, Y., Tanzi, R. E., & Colonna, M.
- Affiliations
- Washington University in St. Louis (US)
- Harvard University (US)
- Yale University (US)
- Corresponding author
- Tanzi, Rudolph E.
- Colonna, Marco
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2016-08-09
- Volume
- 13
- Issue
- 4
- Pages
- 381-387
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC5299056
- OpenAlex
- W2500839489
- Cited by
- 297
- References
- 22
- Citations by year
- 2026: 15 · 2025: 36 · 2024: 22 · 2023: 65 · 2022: 45 · 2021: 31 · 2020: 22 · 2019: 20 · 2018: 26 · 2017: 13 · 2016: 2
- FWCI
- 11.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Eli Lilly and Company
- National Institute of Mental Health (5R01MH060009‐14)
- JPB Foundation (RG4687A1/1)
- National Multiple Sclerosis Society
- Cure Alzheimer's Fund
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- TREM2, Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Cells, Cultured, Family, Humans, Lipoproteins, HDL, Lipoproteins, LDL, Membrane Glycoproteins, Monocytes, Protein Binding, Receptors, Immunologic, Genetic Variation, Cohort Studies, Logistic Models, Genetic Predisposition to Disease, Genetic Association Studies
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
