Microglia and TREM2
Open accessAbstract
TREM2 is a membrane receptor solely expressed on microglia in normal brain. In this review we outline recent advances in TREM2 biology and its implications for microglial function, with particular emphasis on findings from iPSC-derived microglia (iMG) expressing TREM2 loss-of-function mutations. Alterations in receptor proximal and distal signalling underlie TREM2 risk variants linked to neurodegenerative disease, principally NH-linked FTD, and late-onset AD, but emerging data suggest roles for TREM2 in PD, MS and ALS. TREM2 downstream functions include phagocytosis of myelin debris, amyloid beta peptides, and phosphatidylserine-expressing cells (resulting from damage or stress). Microglial survival, migration, DAMP signalling, inflammasome activation, and intercellular signalling including tau spreading via exosomes, as well as roles for sTREM2 in protection and as a biomarker are discussed. The role of TREM2 in metabolic homeostasis, and immunometabolic switching are discussed regarding microglial responses to damage and protection. The use of iPSC models to investigate the role of TREM2 in AD, PD, MS, ALS, and other neurodegenerative diseases could prove invaluable due to their ability to recapitulate human pathology, allowing a full understanding of TREM2 and microglial involvement in the underlying disease mechanisms and progression. This article is part of the Special Issue on "Microglia".
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Inflammation, or neuroinflammation, is a crucial factor in the mechanisms behind AD.
“Inflammation, or neuroinflammation, is a crucial factor in the mechanisms behind AD.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [205]
TREM2 receptor interaction plays a key role in identifying microglia for the build-up of debris and damage during the regulation of microglial activation.
“TREM2 receptor interaction plays a key role in identifying microglia for the build-up of debris and damage during the regulation of microglial activation.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [205]
TREM2 agonists are being investigated as potential therapeutic agents because they reduce inflammation and encourage amyloid-beta microglial phagocytosis.
“TREM2 agonists are being investigated as potential therapeutic agents since they reduce inflammation and encourage amyloid-beta microglial phagocytosis [202,203,204,205].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [205]
In the healthy aging human brain, amyloid-β plaques have the ability to cause persistent inflammation in microglia.
“In the healthy aging human brain, amyloid-β plaques have the ability to cause persistent inflammation in microglia, which are the brain’s resident immune cells.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [205]
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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
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Popescu, A. S., Butler, C. A., Allendorf, D. H., Piers, T. M., Mallach, A., Roewe, J., Reinhardt, P., Cinti, A., Redaelli, L., Boudesco, C., et al. (2022) · Glia · doi:10.1002/glia.24318 · Cited by 53 · see citing works
Cosker, K., Mallach, A., Limaye, J., Piers, T. M., Staddon, J. M., Neame, S. J., Hardy, J., & Pocock, J. M. (2021) · Scientific Reports · doi:10.1038/s41598-021-91207-1 · Cited by 52 · see citing works
Penney, J., Ralvenius, W. T., Loon, A. R., Cerit, O., Dileep, V., Milo, B., Pao, P., Woolf, H., & Tsai, L. (2023) · Glia · doi:10.1002/glia.24485 · Cited by 51 · see citing works
Role of metabolic programming in the modulation of microglia phagocytosis by lipids
Nadjar, A. (2018) · Prostaglandins, Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2018.07.006 · Cited by 49 · see citing works
Singh, H., Rai, V., Nooti, S. K., & Agrawal, D. K. (2021) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2021.1883587 · Cited by 47 · see citing works
TREM2 analysis and increased risk of Alzheimer's disease
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Glebov, K., Wunderlich, P., Karaca, I., & Walter, J. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0479-9 · Cited by 44 · see citing works
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 · see citing works
Profiling TREM2 expression in amyotrophic lateral sclerosis
Jericó, I., Vicuña‐Urriza, J., Blanco‐Luquin, I., Macías, M., Martínez‐Merino, L., Roldán, M., Rojas‐García, R., Pagola, I., Carbayo, Á., de Luna, N., et al. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.01.013 · Cited by 40 · 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
Obst, J., Hall-Roberts, H. L., Smith, T. B., Kreuzer, M., Magno, L., Di Daniel, E., Davis, J. B., & Mead, E. (2021) · Scientific Reports · doi:10.1038/s41598-021-96144-7 · Cited by 36 · see citing works
Peng, G., Qiu, J., Liu, H., Zhou, M., Huang, S., Guo, W., Lin, Y., Chen, X. '., Li, Z., Li, G., et al. (2019) · Journal of Molecular Neuroscience · doi:10.1007/s12031-019-01424-7 · Cited by 27 · see citing works
Sheng, X., Yao, Y., Huang, R., Xu, Y., Zhu, Y., Chen, L., Zhang, L., Wang, W., Zhuo, R., Can, D., et al. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02340-7 · Cited by 27 · see citing works
Mallach, A., Gobom, J., Zetterberg, H., Hardy, J., Piers, T. M., Wray, S., & Pocock, J. M. (2021) · Brain Communications · doi:10.1093/braincomms/fcab009 · Cited by 25 · see citing works
Kiianitsa, K., Kurtz, I., Beeman, N. E., Matsushita, M. M., Chien, W., Raskind, W. H., & Korvatska, O. (2021) · Journal of Leukocyte Biology · doi:10.1002/jlb.2hi0720-463rr · Cited by 25 · see citing works
Ibach, M., Mathews, M., Linnartz‐Gerlach, B., Theil, S., Kumar, S., Feederle, R., Brüstle, O., Neumann, H., & Walter, J. (2020) · Glia · doi:10.1002/glia.23953 · Cited by 24 · see citing works
Dardiotis, E., Rikos, D., Siokas, V., Aloizou, A., Tsouris, Z., Sakalakis, E., Brotis, A. G., Bogdanos, D. P., & Hadjigeorgiou, G. M. (2020) · International Journal of Neuroscience · doi:10.1080/00207454.2020.1750388 · Cited by 23 · see citing works
An Alternatively Spliced TREM2 Isoform Lacking the Ligand Binding Domain is Expressed in Human Brain
Shaw, B. C., Snider, H. C., Turner, A. K., Zajac, D. J., Simpson, J. F., & Estus, S. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-215602 · Cited by 22 · see citing works
Basha, S. C., Ramaiah, M. J., & Rao, K. S. J. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-221070 · Cited by 22 · see citing works
Selection and structural characterization of anti-TREM2 scFvs that reduce levels of shed ectodomain
Szykowska, A., Chen, Y., Smith, T. B., Preger, C., Yang, J., Qian, D., Mukhopadhyay, S. M. M., Wigren, E., Neame, S. J., Gräslund, S., et al. (2021) · Structure · doi:10.1016/j.str.2021.06.010 · Cited by 20 · see citing works
Mallach, A., Gobom, J., Arber, C., Piers, T. M., Hardy, J., Wray, S., Zetterberg, H., & Pocock, J. M. (2021) · Cells · doi:10.3390/cells10112866 · Cited by 18 · see citing works
Pepłońska, B., Berdyński, M., Mandecka, M., Barczak, A. K., Kuźma‐Kozakiewicz, M., Barcikowska, M., & Żekanowski, C. (2018) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2018.1451894 · Cited by 16 · 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
TREM2 as an evolving therapeutic target in Alzheimer’s disease
George, J. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.371360 · Cited by 14 · see citing works
Rikos, D., Siokas, V., Aloizou, A., Tsouris, Z., Aslanidou, P., Koutsis, G., Anagnostouli, M. C., Bogdanos, D. P., Grigoriadis, N., Hadjigeorgiou, G. M., et al. (2019) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2019.07.007 · Cited by 12 · see citing works
Gandy, S., & Ehrlich, M. E. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02895-7 · Cited by 11 · see citing works
Liang, H., Liu, P., Wang, Z., Xiong, H., Yin, C., Dongdong, Z., Wu, C., & Chen, L. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14630 · Cited by 8 · see citing works
Michalski, C., & Wen, Z. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1291115 · Cited by 7 · see citing works
Targeting SHIP1 for therapeutic intervention in Alzheimer’s disease
Obst, J., Bradshaw, W. J., Roberts, H. H., Priestley, R. S., Jimenez‐Antunez, C., Cowley, S. A., Gileadi, O., Mead, E., Daniel, E. D., & Davis, J. B. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.045839 · Cited by 5 · see citing works
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Cited by
Sorted by citations
Neurovascular unit, neuroinflammation and neurodegeneration markers in brain disorders
Kempuraj, D., Dourvetakis, K. D., Cohen, J., Valladares, D. S., Joshi, R. S., Kothuru, S. P., Anderson, T., Chinnappan, B., Cheema, A. K., Klimas, N. G., et al. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1491952 · Cited by 75 · see citing works
Salloway, S., Wojtowicz, J., Voyle, N., Lane, C., Klein, G., Lyons, M., Rossomanno, S., Mazzo, F., Bullain, S., Barkhof, F., et al. (2024) · JAMA Neurology · doi:10.1001/jamaneurol.2024.3937 · Cited by 60 · see citing works
Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease
Thawabteh, A. M., Ghanem, A. W., AbuMadi, S., Thaher, D., Jaghama, W., Karaman, D., & Karaman, R. (2024) · Molecules · doi:10.3390/molecules29215131 · Cited by 56 · 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
He, C., Chen, B., Yang, H., & Zhou, X. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1554398 · Cited by 38 · see citing works
“A different study has shown that TREM2 gene variants strongly associate with AD risk and that TREM2 dysfunction results in microglia’s inability to clear A β plaques and tau proteins effectively (Ameli Mojarad and Ameli Mojarad, 2024; Pocock et al., 2024).”
Hasan, A. R., Tasnim, F., Aktaruzzaman, M., Islam, M. T., Rayhan, R., Brishti, A., Hur, J., Porter, J. E., & Raihan, M. O. (2024) · Neuroglia · doi:10.3390/neuroglia5040027 · Cited by 25 · see citing works
Glial Cell Dynamics in Neuroinflammation: Mechanisms, Interactions, and Therapeutic Implications
García‐Domínguez, M. (2026) · Biomedicines · doi:10.3390/biomedicines14010115 · Cited by 29 · see citing works
“TREM2 is a microglial surface receptor that signals via the adaptor DAP12 (DNAX activating protein of 12 kDa), containing ITAM (immunoreceptor tyrosine-based activation motif) motifs [267].”
TREM 2 in Parkinson’s Disease: A Promising Candidate Gene for Disease Susceptibility and Progression
Alonge, P., Balistreri, C. R., Angelo, T., Magro, D., Rubino, E., & Monastero, R. (2025) · Brain Sciences · doi:10.3390/brainsci15040379 · Cited by 10 · see citing works
“TREM2 is a member of the immunoglobulin superfamily and precisely a transmembrane protein expressed by myeloid cells, such as microglia [7].”
Yuan, M., Nguyen, T. T. T., Gibb, A. J., Xian, Y., & Xu, H. (2025) · Chinese Medicine · doi:10.1186/s13020-025-01204-z · Cited by 8 · see citing works
“Additionally, Aβ accumulation alters receptor expression, triggering a receptor expressed on myeloid cells 2, disrupting microglial activation and phagocytic efficiency [71, 77].”
CSF GPNMB in Parkinson's disease: A potential association with age and microglial activation
Zhu, X., Mizutani, Y., Ohdake, R., Tatebe, H., Maeda, T., Shima, S., Ueda, A., Ito, M., Ito, S., Tokuda, T., et al. (2024) · Journal of Parkinson s Disease · doi:10.1177/1877718x241288712 · Cited by 7 · see citing works
“17 Similarly, the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2), an innate immune receptor found on microglia, 18 is also highly expressed during microglial activation.”
Zhang, X., Wang, R., Pan, X., Chen, Z., Li, Y., Hu, Y., Liu, F., & Cao, X. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-04820-w · Cited by 8 · see citing works
Targeting 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
“TREM2 is a transmembrane glycoprotein that binds to various ligands, such as Aβ, LPS, and apolipopro - teins (Pocock et al., 2024).”
Wang, Y., Wang, Z., Hao, H., Zhao, Y., Wang, J., & Wang, W. (2025) · Toxics · doi:10.3390/toxics13010037 · Cited by 7 · see citing works
“The proteolytic shedding of TREM2 by ADAM10 and ADAM17 can result in the release of sTREM2 [29,30].”
Sharma, A., & Singh, T. G. (2025) · Brain Research · doi:10.1016/j.brainres.2025.150047 · Cited by 6 · see citing works
Cho, S., Zhu, R., Kuncewicz, K., Duan, H., & Gabr, M. T. (2025) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2025.130512 · Cited by 6 · see citing works
Zhao, P., Li, S., Liu, Q., Peng, X.-C., Liu, L., Yang, F.-Y., Wang, C., Qian, F., & Tang, F.-R. (2026) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2026.1726194 · Cited by 5 · see citing works
“…(Hammond et al., 2019), but prolonged activation leads to TREM2 shedding, weakening A β clearance and mediating synapse loss through complement proteins (C1q, C3) (Hong et al., 2016; Shi et al., 2017; Fracassi et al., 2023; Wang et al., 2015; Parhizkar et al., 2019; Pocock et al., 2024).”
Frontiers and hotspots evolution in anti-inflammatory studies for Alzheimer’s disease
Wu, S., Chen, N., & Wang, C. (2024) · Behavioural Brain Research · doi:10.1016/j.bbr.2024.115178 · Cited by 4 · see citing works
Ahmed, S., Bowers, C., Munoz-Martin, J., Jamwal, S., Sanganahalli, B. G., Chen, K., Giuliano, L., Kaswan, Z. A. M., Hyder, F., Yang, X. W., et al. (2026) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2026.106555 · Cited by 4 · see citing works
Jiang, T., Zhai, S., Zheng, T., Chen, X., Wang, L., Wang, Q., & Wang, M. (2025) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-025-04383-6 · Cited by 3 · see citing works
“Moreover, this process leads to the activation of microglia and macrophages, promoting neuroinflammation and oxidative stress (Pukoli and Vécsei 2023), further damaging the myelin sheath and oligodendrocytes (Pocock et al. 2024).”
da Costa, M. D. R., Teixeira, I. M. M., Duque, B. R., Pinheiro, N. M. L., Ananias, C. F., Fernandes, M. O., Silva, L. H. E., Filho, H. L. P., Viana, G. D. A., Magalhães, E. P., et al. (2025) · Exploration of Neuroprotective Therapy · doi:10.37349/ent.2025.1004124 · Cited by 3 · see citing works
Xin, X., Zong, T., Hu, Z., Jin, L., Zhou, W., Sun, J., & Gao, L. (2025) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2025.108934 · Cited by 2 · see citing works
Maeda, T., Mizutani, Y., Ohdake, R., Nagao, R., Kawabata, K., Shima, S., Ueda, A., Ito, M., & Watanabe, H. (2025) · Journal of Neural Transmission · doi:10.1007/s00702-025-03022-x · Cited by 2 · see citing works
Multiple sclerosis: Glial cell activation – Biomarker advances and their translational significance
Zeng, W., Wu, H., & Huang, Y. (2025) · Science Progress · doi:10.1177/00368504251390710 · Cited by 2 · see citing works
Wan, S., Ji, X., Meng, R., & Li, M. N. (2025) · Revista de Neurología · doi:10.31083/rn46121 · Cited by 2 · see citing works
“The TREM2 receptor on the surface of microglia/macrophages can be activated by binding to PtdSer exposed on apoptotic cells [41].”
Ma, L., Zhao, Y. Q., Cai, C., Qs, L., Hu, X., & Wang, L. (2026) · Cells · doi:10.3390/cells15141291 · Cited by 2 · see citing works
“These cells establish a physical barrier between A β plaques and the surrounding neurofibrillary tangles, thus curtailing the propagation of plaques and ameliorating their deleterious effects on adjacent neurons [17].”
Revisiting TREM2: from multi-omics signaling networks to clinical translation
Yang, J., Wan, D., Ren, L., Lv, Y., & Zhao, H. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1782384 · Cited by 2 · see citing works
Navarro, E., & Montesinos, J. (2025) · Contact · doi:10.1177/25152564241312807 · Cited by 2 · see citing works
“Phosphorylated DAP12 recruits and activates spleen tyrosine kinase (SYK) and phospholipase C γ 2, leading to increased intracellular calcium levels and activation of various signaling pathways (Pocock et al., 2024).”
Temporal Dynamics of APOE and TREM2 Expression in Microglial Activation of NMOSD Mouse Models
Xu, S., Dai, W., Wang, T., Cao, S., Du, J., Pang, X., Li, Q., & Tian, Y. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05160-5 · Cited by 2 · see citing works
Visualising the Knowledge Structure of Microglia in Alzheimer’s Disease: A CiteSpace Analysis
Wang, Q., Zhang, X. C., Wang, D., Jiang, X., Zhou, Y., Zhang, T., Yang, X., Liu, L.-Z., & Li, Q. (2025) · Journal of Multidisciplinary Healthcare · doi:10.2147/jmdh.s521350 · Cited by 1 · see citing works
“67,68 The chronic activation of the NLRP3 inflammasome, which is linked to chronic brain inflammation and neuronal loss, has prompted investigations into NLRP3 inhibitors and blockade strategies.”
Geng, X., Yang, H., Wang, Z., Chen, Z., Chen, J., & Yang, M. (2025) · Pathogens · doi:10.3390/pathogens14111105 · Cited by 1 · see citing works
“Previous studies demonstrated that Trem2 expression can be up-regulated through downregulation of ANGPTL2, leading to effective enhancement of autophagy [32,33].”
Zou, F., Ren, X., Huo, G., Liu, P., & Sun, C. (2026) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2026.121683 · Cited by 1 · see citing works
Spinal cord microglia exhibit a dysfunctional response to myelin damage
Zupan, M. C., Petersen, J. M., Stover, A. C., Fairchild, C. A., Mohotti, N. D. S., & Hartley, M. D. (2026) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2026.579022 · Cited by 1 · see citing works
Vasilopoulou, F., Yaman, Ü., Salih, D. A. M., Hardy, J., Wray, S., & Pocock, J. M. (2025) · Research Square · doi:10.21203/rs.3.rs-7487794/v1 · Cited by 1 · see citing works
Neuropharmacology - VSI: Microglia (Editorial)
Loane, D. J., & Lynch, M. A. (2025) · Neuropharmacology · doi:10.1016/j.neuropharm.2025.110505
Cui, L., Yue, Z., Sun, C., & Shao, K. (2026) · Journal of Alzheimer s Disease Reports · doi:10.1177/25424823251411528
“29 Another systematic review highlighted inconsistencies in reported effects of TREM2 on tau pathology.”
Zhang, K., Chi, W., Guo, J., Huang, Y., Zhang, Z., Guo, X., Zhang, B., & Meng, F. (2026) · International Immunopharmacology · doi:10.1016/j.intimp.2026.116269
Soluble TREM2 Is Elevated in Pediatric Patients with Anti-NMDAR Encephalitis
Zhou, A., Ch, R., Zhou, J., Ren, X., & Zhang, W. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15031010
“Triggering receptor expressed on myeloid cells 2 (TREM2) is an immune receptor expressed on the surface of myeloid cells, predominantly expressed by microglia in the central nervous system and plays a crucial role in the immune-related functions of microglial activation [24,25].”
Spinal Cord Microglia Exhibit Impaired Repair Responses to Myelin DamagePreprint
Zupan, M. C., Petersen, J. M., Stover, A. C., Mohotti, N. D. S., & Hartley, M. D. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.23.707565
Xu, Z., & Deng, Y. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-27340-7.00012-7
Effects of Hesperetin Early Intervention on Brain Neurons and Microglia in APPswe/PS1dE9 Mice
Wang, N., Wen, H., Sun, Y., Xu, W., Shen, X., & Wang, R. (2026) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/0118715273418623251203072424
Kong, Z., Shen, L., Ma, D., & Hou, J. (2026) · Clinical and Translational Discovery · doi:10.1002/ctd2.70140
Yang, H., Liu, C., Guo, M., Niu, S., & Xue, Y. (2026) · Research Square · doi:10.21203/rs.3.rs-9618693/v1
Zhao, Y., Wang, W., Li, S., Li, M. T., Zhang, W., Lu, T., Wang, L., Han, T., & Ren, W. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1856481
“…models, triggering receptor expressed on myeloid cells 2 (TREM2) and the fractalkine receptor CX3CR1 have been shown to regulate microglial phagocytosis, in fl ammatory phenotype, and interactions with endothelial cells, thereby impacting angiogenesis and blood-brain barrier integrity (142, 143).”
Mitochondria-associated endoplasmic reticulum membrane (MAM): roles in innate immunity dysregulation
Zhang, Q., Gao, J., Yang, Y., Guo, P., Gao, H., Zhao, S., 张双林, Shi, Y., Xie, G., Han, Y., et al. (2026) · Cell Communication and Signaling · doi:10.1186/s12964-026-03013-9
“…the ligand-binding capacity of the triggering receptor expressed on myeloid cells 2 (TREM2), hindering activation of the downstream DNAX-activating protein of 12 kDa (DAP12)-spleen tyrosine kinase (SYK) signaling pathway and subsequently leading to defective NLRP3 inflammasome activation [71].”
Balaji, P., & Jayaprakash, N. (2026) · SN Comprehensive Clinical Medicine · doi:10.1007/s42399-026-02572-9
“Likewise, microglia are often absent or incompletely represented because they originate from the yolk sac rather than the neuroectoderm, requiring specialized differentiation or co-culture strategies for successful incorporation [111].”
Fuchs, N. S., Yuan, S., Kuncewicz, K., Elhamouly, M. A., Gaamouch, F. E., & Gabr, M. T. (2026) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.6c00304
Decoding TREM2: A microglial receptor governing the fate of myelin
Zhang, Z., Zhang, W., Jin, L., Wei, C., Chen, H., 程相树, & Wei, J. (2026) · Cellular Signalling · doi:10.1016/j.cellsig.2026.112815
Wu, Y., Duan, L., Zhang, L., Wang, S., Yan, H., He, M., Wang, T., Li, L., & Gao, Y. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1912989
“Among cell-based approaches, iPSC-derived microglia have emerged as valuable platforms for modeling TREM2 de fi ciency and evaluating functional rescue strategies (178).”
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Lv, Y., Shi, M., Zhao, Y., Yu, Y., Jia, W., & Hai, Z. (2026) · Clinical and Translational Medicine · doi:10.1002/ctm2.70863
“69 Experimental models of AD demonstrate that loss of functional TREM2 leads to exaggerated neuroinflammatory responses and defective resolution of inflammation.”
Samantaray, P., & Verma, P. (2026) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2026.104130
- Authors
- Pocock, J., Vasilopoulou, F., Svensson, E., & Cosker, K.
- Affiliations
- UCL Queen Square Institute of Neurology (GB)
- Corresponding author
- Pocock, Jennifer
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2024-10
- Volume
- 257
- Pages
- 110020
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W4399143329
- Cited by
- 54
- References
- 111
- Citations by year
- 2026: 27 · 2025: 20 · 2024: 7
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- green
- discovery.ucl.ac.uk
- Licence
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Rosetrees Trust
- Eisai
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- TREM2, microglia, iPSC-derived microglia, neurodegenerative diseases, frontotemporal dementia, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, phagocytosis, myelin debris, amyloid-beta, phosphatidylserine, inflammasome, tau propagation, exosomes, soluble TREM2, biomarkers, metabolic homeostasis, microglial migration, microglial survival
- MeSH terms
- Animals, Humans, Membrane Glycoproteins, Phagocytosis, Receptors, Immunologic, Microglia, Neurodegenerative Diseases, Induced Pluripotent Stem Cells
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