TREM2 promotes Aβ phagocytosis by upregulating C/EBPα-dependent CD36 expression in microglia
Open accessAbstract
TREM2 plays a critical role in the alleviation of Alzheimer’s disease by promoting Aβ phagocytosis by microglia, but the detailed molecular mechanism underlying TREM2-induced direct phagocytic activity of Aβ remains to be revealed. We found that learning and memory functions were improved in aged TREM2 TG mice, with the opposite effects in KO mice. The amount of phagocytosed Aβ was significantly reduced in the primary microglia of KO mice. CD36 expression in primary microglia was greater in TG than in WT mice but was substantially decreased in KO mice. The expression of C/EBPα, an upstream transcriptional activator of CD36, was also elevated in primary microglia of TG mice but decreased in KO mice. The transcription of CD36 was markedly increased by TREM2 overexpression, and this effect was suppressed by a mutation of the C/EBPα binding site on the CD36 promoter. The TREM2-induced expression of CD36 and C/EBPα was inhibited by treatment with PI3K/AKT signaling blockers, and phosphorylation of AKT was elevated in TREM2-overexpressing BV2 cells. The present study provides evidence that TREM2 is required for preventing loss of memory and learning in Alzheimer’s disease by regulating C/EBPα-dependent CD36 expression and the consequent Aβ phagocytosis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Lack of Trem2 reduces chemotaxis and phagocytosis of microglia.
“Furthermore, lack of Trem2 reduces chemotaxis and phagocytosis of microglia (54, 55).”
From Deletion of <i>Abi3</i> gene locus exacerbates neuropathological features of Alzheimer’s disease in a mouse model of Aβ amyloidosis (2021) · cites this paper as [54]
The Results section reports reduced Aβ phagocytosis in TREM2-knockout microglia. The Discussion also describes reduced microglial migration with TREM2 deficiency, but it does not establish reduced chemotaxis specifically (directed movement toward a chemical cue). (LLM, conf=0.83)
Experimental — accuracy not yet measuredTrem2 activates multiple signaling pathways involved in actin cytoskeleton organization.
“It was also demonstrated that Trem2 activates multiple signaling pathways involved in actin cytoskeleton organization (54).”
From Deletion of <i>Abi3</i> gene locus exacerbates neuropathological features of Alzheimer’s disease in a mouse model of Aβ amyloidosis (2021) · cites this paper as [54]
The Introduction (page unavailable) says TREM2 signaling proceeds through multiple mediators, including PI3K, AKT and ERK. Neither that passage nor the searched passages on actin and cytoskeletal remodeling link those pathways to actin cytoskeleton organization, so that part of the claim is unsupported by our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359 · see citing works
Lambert, M. P., Barlow, A. K., Chromy, B. A., Edwards, C., Freed, R., Liosatos, M., Morgan, T. E., Rozovsky, I., Trommer, B., Viola, K. L., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6448 · Cited by 3,506 · see citing works
Alzheimer Mechanisms and Therapeutic Strategies
Huang, Y., & Mucke, L. (2012) · Cell · doi:10.1016/j.cell.2012.02.040 · Cited by 1,758 · see citing works
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 · see citing works
Soluble Amyloid β Peptide Concentration as a Predictor of Synaptic Change in Alzheimer's Disease
Lue, L.-F., Kuo, Y.-M., Roher, A. E., Brachova, L., Shen, Y., Sue, L., Beach, T., Kurth, J. H., Rydel, R. E., & Rogers, J. (1999) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65184-x · Cited by 1,530 · see citing works
CD36 is a receptor for oxidized low density lipoprotein
Endemann, G., Stanton, L. W., Madden, K. S., Bryant, C. M., White, R. T., & Protter, A. A. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)50272-1 · Cited by 1,282 · see citing works
Lacor, P. N., Buniel, M. C., Furlow, P. W., Sanz Clemente, A., Velasco, P. T., Wood, M., Viola, K. L., & Klein, W. L. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3501-06.2007 · Cited by 1,188 · see citing works
Takahashi, K., Rochford, C. D. P., & Neumann, H. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041611 · Cited by 1,124 · see citing works
Activation of the innate immune receptor Dectin-1 upon formation of a ‘phagocytic synapse’
Goodridge, H. S., Reyes, C. N., Becker, C. A., Katsumoto, T. R., Ma, J., Wolf, A. J., Bose, N., Chan, A. S. H., Magee, A. S., Danielson, M. E., et al. (2011) · Nature · doi:10.1038/nature10071 · Cited by 871 · 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
Microglia derived from aging mice exhibit an altered inflammatory profile
Sierra, A., Gottfried‐Blackmore, A. C., McEwen, B. S., & Bulloch, K. (2007) · Glia · doi:10.1002/glia.20468 · Cited by 688 · see citing works
Paloneva, J., Manninen, T., Christman, G., Hovanes, K., Mandelin, J., Adolfsson, R., Bianchin, M., Bird, T., Miranda, R., Salmaggi, A., et al. (2002) · The American Journal of Human Genetics · doi:10.1086/342259 · Cited by 683 · see citing works
Phagocytosis of Microglia in the Central Nervous System Diseases
Fu, R., Shen, Q., Xu, P., Luo, J. J., & Tang, Y. (2014) · Molecular Neurobiology · doi:10.1007/s12035-013-8620-6 · Cited by 646 · see citing works
Identification of glycoprotein IV (CD36) as a primary receptor for platelet-collagen adhesion
Tandon, N. N., Kralisz, U., & Jamieson, G. A. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)83273-2 · Cited by 491 · see citing works
CD36 Mediates the Innate Host Response to β-Amyloid
El Khoury, J. B., Moore, K. J., Means, T. K., Leung, J., Terada, K., Toft, M., Freeman, M. W., & Luster, A. D. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021546 · Cited by 483 · see citing works
Synthetic amyloid-β oligomers impair long-term memory independently of cellular prion protein
Balducci, C., Beeg, M., Stravalaci, M., Bastone, A., Sclip, A., Biasini, E., Tapella, L., Colombo, L., Manzoni, C., Borsello, T., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911829107 · Cited by 466 · see citing works
TREM2- and DAP12-dependent activation of PI3K requires DAP10 and is inhibited by SHIP1
Peng, Q., Malhotra, S., Torchia, J. A., Kerr, W. G., Coggeshall, K. M., & Humphrey, M. B. (2010) · Science Signaling · doi:10.1126/scisignal.2000500 · Cited by 413 · see citing works
Kawabori, M., Kacimi, R., Kauppinen, T., Calosing, C., Kim, J. Y., Hsieh, C. L., Nakamura, M. C., & Yenari, M. A. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2620-14.2015 · Cited by 375 · see citing works
Lucin, K. M., O’Brien, C. E., Bieri, G., Czirr, E., Mosher, K. I., Abbey, R. J., Mastroeni, D. F., Rogers, J., Spencer, B., Masliah, E., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.06.046 · Cited by 374 · see citing works
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
DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features
Paloneva, J., Mandelin, J., Kiialainen, A., Böhling, T., Prudlo, J., Hakola, P., Haltia, M., Konttinen, Y. T., & Peltonen, L. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030027 · Cited by 318 · see citing works
Impaired Synaptic Function in the Microglial KARAP/DAP12-Deficient Mouse
Roumier, A., Béchade, C., Poncer, J. C., Smalla, K., Tomasello, E., Vivier, É., Gundelfinger, E. D., Triller, A., & Bessis, A. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.2251-04.2004 · Cited by 228 · see citing works
TREM2 deficiency reduces the efficacy of immunotherapeutic amyloid clearance
Xiang, X., Werner, G., Bohrmann, B., Liesz, A., Mazaheri, F., Capell, A., Feederle, R., Knuesel, I., Kleinberger, G., & Haass, C. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606370 · Cited by 183 · see citing works
Specific lipid recognition is a general feature of CD300 and TREM molecules
Cannon, J. P., O’Driscoll, M., & Litman, G. W. (2011) · Immunogenetics · doi:10.1007/s00251-011-0562-4 · Cited by 162 · see citing works
McBindall—A Better Name for CCAAT/Enhancer Binding Proteins?
McKnight, S. L. (2001) · Cell · doi:10.1016/s0092-8674(01)00543-8 · Cited by 152 · see citing works
Park, M. S., Yi, J., Kim, E. M., Yoon, I.-J., Lee, E. H., Lee, H.-Y., Ji, K.-Y., Lee, K. H., Jang, J.-H., Oh, S.-S., et al. (2014) · Diabetes · doi:10.2337/db13-1869 · Cited by 85 · see citing works
Self-citationQiao, L., Zou, C., Shao, P., Schaack, J. B., Johnson, P. F., & Shao, J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800055200 · Cited by 65 · see citing works
Processing of Amyloid Precursor Protein and Amyloid Peptide Neurotoxicity
Pierrot, N., & Jean-Noël, O. (2008) · Current Alzheimer Research · doi:10.2174/156720508783954721 · Cited by 60 · see citing works
Transgenic Mice as a Model for Alzheimers Disease
Lithner, C. U., Hedberg, M. M., & Nordberg, A. K. (2011) · Current Alzheimer Research · doi:10.2174/156720511798192736 · Cited by 34 · see citing works
Natural Amyloid-Beta Oligomers Acutely Impair the Formation of a Contextual Fear Memory in Mice
Kittelberger, K. A., Piazza, F., Tesco, G., & Reijmers, L. G. J. E. (2012) · PLoS ONE · doi:10.1371/journal.pone.0029940 · Cited by 32 · see citing works
Ge, J. (2004) · World Journal of Gastroenterology · doi:10.3748/wjg.v10.i21.3141 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Inflammation: the link between comorbidities, genetics, and Alzheimer’s disease
Newcombe, E. A., Camats-Perna, J., Silva, M. L., Valmas, N., Huat, T. J., & Medeiros, R. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1313-3 · Cited by 532 · see citing works
Beyond the neuron–cellular interactions early in Alzheimer disease pathogenesis
Henstridge, C. M., Hyman, B. T., & Spires-Jones, T. L. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0113-1 · Cited by 348 · see citing works
Phagocytosis in the Brain: Homeostasis and Disease
Galloway, D. A., Phillips, A. E. M., Owen, D. R., & Moore, C. S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00790 · Cited by 304 · see citing works
Wang, X., He, Q., Zhou, C., Xu, Y., Liu, D., Fujiwara, N., Kubota, N., Click, A., Henderson, P., Vancil, J., et al. (2023) · Immunity · doi:10.1016/j.immuni.2022.11.013 · Cited by 262 · see citing works
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 · 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
Dysregulated phosphoinositide 3-kinase signaling in microglia: shaping chronic neuroinflammation
Chu, E., Mychasiuk, R., Hibbs, M. L., & Semple, B. D. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02325-6 · Cited by 152 · see citing works
Microglia in Alzheimer’s Disease: A Target for Therapeutic Intervention
Zhang, G., Wang, Z., Hu, H., Zhao, M., & Sun, L. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.749587 · Cited by 132 · see citing works
TREM2: Potential therapeutic targeting of microglia for Alzheimer's disease
Li, Y., Xu, H., Wang, H., Yang, K., Luan, J., & Wang, S. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115218 · Cited by 128 · see citing works
McMenamin, P. G., Saban, D. R., & Dando, S. J. (2019) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2018.12.002 · Cited by 115 · see citing works
The innate immune system in diabetic retinopathy
Pan, W. W., Lin, F., & Fort, P. E. (2021) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2021.100940 · Cited by 115 · see citing works
TREM2 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 · see citing works
TREM2 promotes cholesterol uptake and foam cell formation in atherosclerosis
Guo, X. Q., Li, B., Wen, C., Zhang, F. S., Xiang, X., Nie, L., Chen, J., & Mao, L. (2023) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-04786-9 · Cited by 96 · see citing works
TREM Receptors Connecting Bowel Inflammation to Neurodegenerative Disorders
Natale, G., Biagioni, F., Busceti, C. L., Gambardella, S., Limanaqi, F., & Fornai, F. (2019) · Cells · doi:10.3390/cells8101124 · Cited by 82 · see citing works
Immune Activation in Alzheimer Disease
Mary, A., Mancuso, R., & Heneka, M. T. (2024) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101921-035222 · Cited by 79 · see citing works
Efficacy and mechanism of cGAMP to suppress Alzheimer’s disease by elevating TREM2
Xu, Q., Xu, W., Cheng, H., Yuan, H., & Tan, X. (2019) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2019.07.004 · Cited by 75 · see citing works
AmeliMojarad, M., & AmeliMojarad, M. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14856 · Cited by 73 · see citing works
Koronyo‐Hamaoui, M., Sheyn, J., Hayden, E. Y., Li, S., Fuchs, D.-T. S., Regis, G. C., Lopes, D. H. J., Black, K. L., Bernstein, K. E., Teplow, D. B., et al. (2019) · Brain · doi:10.1093/brain/awz364 · Cited by 70 · see citing works
Trem2 Y38C mutation and loss of Trem2 impairs neuronal synapses in adult mice
Jadhav, V., Lin, P. B., Pennington, T., Prisco, G. V. D., Jannu, A. J., Xu, G., Moutinho, M., Zhang, J., Atwood, B. K., Puntambekar, S. S., et al. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00409-0 · Cited by 69 · see citing works
Gedam, M., Comerota, M. M., Propson, N. E., Chen, T., Jin, F., Wang, M. C., & Zheng, H. (2023) · Journal of Clinical Investigation · doi:10.1172/jci167501 · Cited by 71 · see citing works
Aged Mouse Cortical Microglia Display an Activation Profile Suggesting Immunotolerogenic Functions
Zöller, T., Attaai, A., Potru, P. S., Ruß, T., & Spittau, B. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030706 · Cited by 66 · 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 · see citing works
TREM2 ‐dependent microglial function is essential for remyelination and subsequent neuroprotection
Wang, Y., Kyauk, R. V., Shen, Y. A., Xie, L., Reichelt, M., Lin, H., Jiang, Z., Ngu, H., Shen, K., Greene, J. J., et al. (2023) · Glia · doi:10.1002/glia.24335 · Cited by 56 · see citing works
Wang, L., Nykänen, N.-P., Western, D., Gorijala, P., Timsina, J., Li, F., Wang, Z., Ali, M., Yang, C., Liu, M., et al. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00687-4 · Cited by 58 · see citing works
Canepa, E., Parodi‐Rullán, R. M., Vázquez‐Torres, R., Gamallo‐Lana, B., Guzman‐Hernandez, R. A., Lemon, N. L., Angiulli, F., Debure, L., Ilies, M. A., Østergaard, L., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13063 · Cited by 52 · see citing works
IL-4 and IL-10 promotes phagocytic activity of microglia by up-regulation of TREM2
Yi, S., Jiang, X., Tang, X., Li, Y., Xiao, C., Zhang, J., & Zhou, T. (2020) · Cytotechnology · doi:10.1007/s10616-020-00409-4 · Cited by 48 · see citing works
White matter-associated microglia: New players in brain aging and neurodegenerative diseases
Ahn, K., Lee, S., & Mook‐Jung, I. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101574 · Cited by 46 · see citing works
Self-citationRecent Insights Into the Role of Macrophages in Acute Gout
Liu, L., Zhu, L., Liu, M., Zhao, L., Yu, Y., Yu, X., & Shan, L. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.955806 · Cited by 47 · see citing works
New insight on microglia activation in neurodegenerative diseases and therapeutics
Xu, Y., Gao, W., Sun, Y., & Wu, M. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1308345 · Cited by 49 · see citing works
Mishra, P. K., Palma, M., Buechel, B., Moore, J., Davra, V., Chu, N., Millman, A., Hallab, N. J., Kanneganti, T., Birge, R. B., et al. (2019) · Nature Materials · doi:10.1038/s41563-018-0271-6 · Cited by 44 · see citing works
Electroacupuncture ameliorates neuroinflammation in animal models
Xin, Y., Wang, J.-X., & Xu, A. (2022) · Acupuncture in Medicine · doi:10.1177/09645284221076515 · Cited by 43 · see citing works
An emerging role for microglia in stress‐effects on memory
Sanguino‐Gómez, J., Buurstede, J. C., Abiega, O., Fitzsimons, C. P., Lucassen, P. J., Eggen, B. J. L., Lesuis, S. L., Meijer, O. C., & Krugers, H. J. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.15188 · Cited by 43 · see citing works
TREM2 Acts as a Tumor Suppressor in Colorectal Carcinoma through Wnt1/β-catenin and Erk Signaling
Kim, S., Kim, E.-M., Ji, K.-Y., Lee, H.-Y., Yee, S., Woo, S.-M., Yi, J., Yun, C., Choi, H., & Kang, H. (2019) · Cancers · doi:10.3390/cancers11091315 · Cited by 43 · see citing works
Self-citationOrigin and function of synovial macrophage subsets during inflammatory joint disease
Culemann, S., Grüneboom, A., & Krönke, G. (2019) · Advances in immunology · doi:10.1016/bs.ai.2019.08.006 · Cited by 41 · see citing works
Roles of TREM2 in the Pathological Mechanism and the Therapeutic Strategies of Alzheimer's Disease
Lin, M., Yu, J., Zhang, W., Lao, F., & Huang, H. (2024) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2024.164 · Cited by 41 · see citing works
Blood-brain barrier and innate immunity in the pathogenesis of Alzheimer's disease
Šimić, G., Španić, E., Horvat, L. L., & Hof, P. R. (2019) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2019.06.003 · Cited by 39 · see citing works
Immune Regulatory Functions of Macrophages and Microglia in Central Nervous System Diseases
Poppell, M., Hammel, G., & Ren, Y. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065925 · Cited by 38 · see citing works
Liang, F., Huang, T., Li, B., Zhao, Y., Zhang, X., & Xu, B. (2020) · Neuroreport · doi:10.1097/wnr.0000000000001429 · Cited by 38 · see citing works
Zhou, H., Li, J., Hu, L., Yu, J., Fu, X., Liang, F., Yan, F., & Chen, G. (2022) · Journal of Advanced Research · doi:10.1016/j.jare.2022.03.011 · Cited by 36 · see citing works
Avenanthramide-C Restores Impaired Plasticity and Cognition in Alzheimer’s Disease Model Mice
Ramasamy, V. S., Samidurai, M., Park, H. J., Wang, M., Park, R. Y., Yu, S. Y., Kang, H. K., Hong, S., Choi, W., Lee, Y., et al. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-01707-5 · Cited by 37 · see citing works
Self-citationThe Past and Present Lives of the Intraocular Transmembrane Protein CD36
Yang, R., Liu, Q., & Zhang, M. (2022) · Cells · doi:10.3390/cells12010171 · Cited by 37 · see citing works
Microglial TREM2 at the Intersection of Brain Aging and Alzheimer’s Disease
Qu, W., & Li, L. (2021) · The Neuroscientist · doi:10.1177/10738584211040786 · Cited by 37 · see citing works
Althafar, Z. M. (2022) · Molecules · doi:10.3390/molecules27134124 · Cited by 35 · see citing works
The emerging role of brain neuroinflammatory responses in Alzheimer’s disease
AmeliMojarad, M., AmeliMojarad, M., & Cui, X. (2024) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2024.1391517 · Cited by 33 · see citing works
Ernest James Phillips, T., & Maguire, E. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.652593 · Cited by 33 · see citing works
Ni, J., Xie, Z., Quan, Z., Meng, J., & Qing, H. (2023) · Glia · doi:10.1002/glia.24465 · Cited by 33 · see citing works
Unravelling the glial response in the pathogenesis of Alzheimer's disease
Alibhai, J. D., Diack, A. B., & Manson, J. C. (2018) · The FASEB Journal · doi:10.1096/fj.201801360r · Cited by 31 · see citing works
Comerota, M. M., Gedam, M., Xiong, W., Jin, F., Deng, L., Wang, M. C., Wang, J., & Zheng, H. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00648-x · Cited by 31 · see citing works
Ganz, T., Fainstein, N., Elad, A., Lachish, M., Goldfarb, S., Einstein, O., & Ben‐Hur, T. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02369-8 · Cited by 30 · see citing works
Autophagy & Phagocytosis in Neurological Disorders and their Possible Cross-talk
Li, G., Sherchan, P., Tang, Z., & Tang, J. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666210407150632 · Cited by 29 · see citing works
Cellular Biology of Tau Diversity and Pathogenic Conformers
Kang, S., Eskandari‐Sedighi, G., Hromádková, L., Safar, J., & Westaway, D. A. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.590199 · Cited by 27 · see citing works
Pfänder, P., Fidan, M., Burret, U., Lipinski, L., & Vettorazzi, S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01554 · Cited by 24 · see citing works
Ennerfelt, H. E., & Lukens, J. R. (2023) · Clinical and Translational Medicine · doi:10.1002/ctm2.1178 · Cited by 22 · see citing works
Wang, Y., Bao, D., Xu, B., Cheng, C., Dong, Y., Wei, X., & Niu, C. (2019) · Neural Regeneration Research · doi:10.4103/1673-5374.250620 · Cited by 22 · see citing works
Takatori, S., Kondo, M., & Tomita, T. (2025) · Inflammation and Regeneration · doi:10.1186/s41232-025-00383-4 · Cited by 23 · see citing works
Differential interaction with TREM2 modulates microglial uptake of modified Aβ species
Joshi, P., Riffel, F., Satoh, K., Enomoto, M., Qamar, S., Scheiblich, H., Villacampa, N., Kumar, S., Theil, S., Parhizkar, S., et al. (2021) · Glia · doi:10.1002/glia.24077 · Cited by 20 · see citing works
Wang, X., Xie, Y., Fan, X., Wu, X., Wang, D., & Li, Z. (2024) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01489-6 · Cited by 22 · see citing works
Simons, E. S., Smith, M. A., Crish, S. D., & Crish, S. D. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105146 · Cited by 19 · see citing works
Survival motor neuron protein deficiency alters microglia reactivity
Khayrullina, G., Alipio‐Gloria, Z. A., Deguise, M., Gagnon, S., Chehadé, L., Stinson, M. W., Belous, N., Bergman, E. M., Lischka, F. W., Rotty, J. D., et al. (2022) · Glia · doi:10.1002/glia.24177 · Cited by 18 · see citing works
Novel Anti-Neuroinflammatory Properties of a Thiosemicarbazone–Pyridylhydrazone Copper(II) Complex
Choo, X. Y., McInnes, L. E., Grubman, A., Wasielewska, J. M., Belaya, I., Burrows, E. L., Quek, H., Cañas-Martín, J., Loppi, S. H., Sorvari, A., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810722 · Cited by 19 · see citing works
Bonomi, C. G., Assogna, M., Donna, M. G. D., Bernocchi, F., Lucia, V. D., Nuccetelli, M., Fiorelli, D., Loizzo, S., Mercuri, N. B., Koch, G., et al. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-221010 · Cited by 20 · see citing works
The Role of TREML2 in Alzheimer’s Disease
Wang, S., Gong, P., Yan, E., Zhang, Y., & Jiang, T. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200406 · Cited by 18 · see citing works
Sepulveda, J., Kim, J. Y., Binder, J., Vicini, S., & Rebeck, G. W. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00714-y · Cited by 19 · see citing works
Guo, X., Liu, Y., Morgan, D., & Zhao, L. (2020) · Aging and Disease · doi:10.14336/ad.2020.0201 · Cited by 16 · see citing works
Jagadeesan, N., Roules, G. C., Chandrashekar, D. V., Yang, J., Kolluru, S., & Sumbria, R. K. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05008-x · Cited by 18 · see citing works
SHIP inhibition mediates select TREM2-induced microglial functions
Ramakrishnan, G. S., Berry, W. L., Pacherille, A., Kerr, W. G., Chisholm, J. D., Pedicone, C., & Humphrey, M. B. (2024) · Molecular Immunology · doi:10.1016/j.molimm.2024.04.002 · Cited by 17 · see citing works
MAVS signaling shapes microglia responses to neurotropic virus infection
Gern, O. L., Pavlou, A., Mulenge, F., Busker, L. M., Ghita, L., Aringo, A., Costa, B., Spanier, J., Waltl, I., Stangel, M., et al. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03258-6 · Cited by 15 · see citing works
Liu, L.-C., Liang, J.-Y., Liu, Y.-H., Liu, B., Dong, X.-H., Cai, W.-H., & Zhang, N. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e30523 · Cited by 15 · see citing works
RetractedThe role of microglial TREM2 in development: A path toward neurodegeneration?
Matteoli, M. (2024) · Glia · doi:10.1002/glia.24574 · Cited by 16 · see citing works
Danziger, R., Fuchs, D.-T. S., Koronyo, Y., Rentsendorj, A., Sheyn, J., Hayden, E. Y., Teplow, D. B., Black, K. L., Fuchs, S., Bernstein, K. E., et al. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1179315 · Cited by 13 · see citing works
Boudesco, C., Nonneman, A., Cinti, A., Picardi, P., Redaelli, L., Swijsen, S., Roewe, J., Reinhardt, P., Ibach, M., Walter, J., et al. (2022) · Glia · doi:10.1002/glia.24252 · Cited by 14 · see citing works
Jin, N., Sha, W., & Gao, L. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.741368 · Cited by 14 · see citing works
The various roles of TREM2 in cardiovascular disease
Wang, S., Cao, C., & Peng, D. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1462508 · Cited by 13 · see citing works
Njoku, G. C., & Kanmogne, G. D. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26189069 · Cited by 15 · see citing works
Watson, Z., & Tang, S. (2022) · Cells · doi:10.3390/cells11121943 · Cited by 13 · see citing works
The Pathogenesis in Alzheimer's Disease: TREM2 as a Potential Target
Liu, G., Zhang, L., Fan, Y., & Ji, W. (2023) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2206150 · Cited by 13 · see citing works
Su, P., Zhang, J., Wu, J., Chen, H., Luo, W., & Hu, M. (2023) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2023.115058 · Cited by 13 · see citing works
Macrophage heterogeneity and plasticity in liver injury and repair mechanisms
Zhang, T., Horn, P., Peiseler, M., & Tacke, F. (2025) · Stem Cells · doi:10.1093/stmcls/sxaf072 · Cited by 13 · see citing works
Connor, S. M., Rashid, M., Ryan, K. J., Patel, K. R., Boyd, J. D., Smith, J., Elyaman, W., Bennett, D. A., & Bradshaw, E. M. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.894601 · Cited by 12 · see citing works
Biomaterials in Alzheimer's Disease: An Anti‐Neuroinflammatory Perspective
Huang, N., Huang, W., Wang, M., Shi, J., Luo, Y., & Huang, J. (2025) · Advanced Healthcare Materials · doi:10.1002/adhm.202500498 · Cited by 13 · see citing works
Roles of Microglia in AD Pathology
Gao, R., Wu, H., Li, Q., & Zhao, J. (2023) · Current Alzheimer Research · doi:10.2174/1567205020666230203112351 · Cited by 10 · see citing works
Wang, X., Liu, L., Jiang, X., Saredy, J., Xi, H., Cueto, R., Sigler, D., Khan, M., Wu, S., Ji, Y. H., et al. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-023-01311-9 · Cited by 8 · see citing works
Lin, Y.-Y., Chang, W.-H., Hsieh, S.-L. E., & Cheng, I. H.-J. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03253-x · Cited by 10 · see citing works
Schwarz, H., Bässler, S., Balta, D., Socher, E., Zunke, F., & Arnold, P. (2022) · Behavioural Brain Research · doi:10.1016/j.bbr.2022.113977 · Cited by 8 · see citing works
Li, H., Zhang, Q., Xue, X., Zhang, J., Wang, S., Zhang, J., Li, L., & Niu, Q. L. (2023) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2023.115062 · Cited by 8 · see citing works
Liu, J., Zhou, J., You, C., Xia, H., Gao, Y., Liu, Y., & Gong, X. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1435082 · Cited by 9 · see citing works
Hidden features: CD36/SR-B2, a master regulator of macrophage phenotype/function through metabolism
Chen, Y., Zhang, X., Huang, S., & Febbraio, M. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1468957 · Cited by 8 · see citing works
Jang, B.-K., Shin, S. J., Park, H. H., Kumar, V., Park, Y., Kim, J. Y., Kang, H., Park, S. Y., Kwon, Y., Shin, S.-E., et al. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics17010013 · Cited by 7 · see citing works
Self-citationTargeting Microglial Activation to Modulate Neuroinflammation in Alzheimer’s Disease
Patil, V., Sharma, A., Parekh, B. K., Farah, H., Jyothi, S. R., Mishra, S. S., Nanda, A., Al-Hasnaawei, S., & Mishra, M. K. (2025) · NeuroMolecular Medicine · doi:10.1007/s12017-025-08898-2 · Cited by 9 · see citing works
Gallo, C., Verrillo, L., Manzo, E., Cauzzi, E., Barbera, L. L., Sabatino, G., Paolis, M. L. D., Sciacca, M. F. M., Barra, G., Peroni, E., et al. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03634-w · Cited by 8 · see citing works
Axl is a key regulator of intestinal γδ T‐cell homeostasis
Kim, S., Park, M. J., Yee, S., Ji, K.-Y., Lee, E., Nguyen, T., Nguyen, T. H., Jang, J. H., Kim, E., Choi, H., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201901356r · Cited by 7 · see citing works
Self-citationSynergistic potential of TREM2 agonists and exercise training in Alzheimer’s disease
Zhang, J., Schneider, B. A., Muguerza, E., Chung, E. K., & Hsu, C. G. (2026) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00124.2025 · Cited by 6 · see citing works
Yang, A., Chen, Y., Gao, Y., Lv, Q., Li, Y., Li, F., Yu, R., Han, Z., Dai, S., Zhu, J., et al. (2024) · Food & Function · doi:10.1039/d4fo00215f · Cited by 6 · see citing works
Wang, Y., & Han, B. (2022) · Combinatorial Chemistry & High Throughput Screening · doi:10.2174/1386207325666220726163514 · Cited by 6 · see citing works
Genomic analyses reveal new insights into Alzheimer's diseasePreprint
Uffelmann, E., Wightman, D. P., Bahrami, S., Shadrin, A. A., Fominykh, V., Ojima, T., Jiang, C., Benner, C., Moreno, E., Campos, A. I., et al. (2025) · medRxiv · doi:10.1101/2025.10.10.25337470 · Cited by 7 · see citing works
Chen, B., Lu, H.-C., Huang, L., Wang, J., Bujold, M., Tang, L., Du, X., & Wang, Y. (2026) · Journal of Neuroinflammation · doi:10.1186/s12974-026-03733-2 · Cited by 5 · see citing works
Paul, D., & Basavan, D. (2022) · Future Journal of Pharmaceutical Sciences · doi:10.1186/s43094-022-00446-0 · Cited by 5 · see citing works
Kim, J. E., & Leem, J. Y. (2021) · Korean Journal of Medicinal Crop Science · doi:10.7783/kjmcs.2021.29.5.337 · Cited by 4 · see citing works
Yang, F., Kong, X., Hu, Y., Liu, W.-Z., Xie, P.-F., Gu, Y., Zhang, Y., Yang, Y., Tang, C.-F., & Li, J.-M. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.08.050 · Cited by 7 · see citing works
High Content Imaging and Quantification of Microglia Phagocytosis In Vitro
McPherson, C. A., Kelly‐Rajan, K., d’Hellencourt, C. L., & Harry, G. J. (2023) · Current Protocols · doi:10.1002/cpz1.638 · Cited by 3 · see citing works
- Authors
- Kim, S.-M., Mun, B.-R., Lee, S.-J., Joh, Y., Lee, H.-Y., Ji, K.-Y., Choi, H.-R., Lee, E.-H., Kim, E.-M., Jang, J.-H., Song, H.-W., Mook-Jung, I., Choi, W.-S., & Kang, H.-S.
- Affiliations
- Chonnam National University (KR)
- Daegu-Gyeongbuk Medical Innovation Foundation (KR)
- Nambu University (KR)
- Korea Atomic Energy Research Institute (KR)
- Korea Institute of Toxicology (KR)
- Corresponding author
- Choi, Won-Seok
- Kang, Hyung-Sik
- Venue
- Scientific Reports
- Published
- 2017-09-11
- Volume
- 7
- Issue
- 1
- Pages
- 11118-11118
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5593901
- OpenAlex
- W2751088224
- Cited by
- 143
- References
- 32
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 38 · 2023: 23 · 2022: 18 · 2021: 13 · 2020: 9 · 2019: 13 · 2018: 4
- FWCI
- 3.54
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Research Foundation
- National Research Foundation of Korea (2016R1D1A3B03931710)
- 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
- TREM2, amyloid-beta phagocytosis, microglia, CD36, C/EBPα, Alzheimer's disease, learning and memory, PI3K/Akt signaling, Akt phosphorylation, TREM2 knockout mice
- MeSH terms
- Animals, Immunohistochemistry, Membrane Glycoproteins, Mice, Transgenic, Neurons, Phagocytes, Phagocytosis, Receptors, Immunologic, Biomarkers, Gene Expression Regulation, Neoplastic, Amyloid beta-Peptides, Microglia, Mice, Knockout, CD36 Antigens, CCAAT-Enhancer-Binding Proteins, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
