Cited by 496Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

The DOI matches its Crossref record; 166 of the 166 references it cites were found in a registry or an index.

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

Open access

Gratuze, Maud, Leyns, Cheryl E. G., Holtzman, David M.·2018·Molecular Neurodegeneration

DOI 10.1186/s13024-018-0298-9PMC PMC6302500

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Abstract

Alzheimer's disease (AD) is the leading cause of dementia. The two histopathological markers of AD are amyloid plaques composed of the amyloid-β (Aβ) peptide, and neurofibrillary tangles of aggregated, abnormally hyperphosphorylated tau protein. The majority of AD cases are late-onset, after the age of 65, where a clear cause is still unknown. However, there are likely different multifactorial contributors including age, enviornment, biology and genetics which can increase risk for the disease. Genetic predisposition is considerable, with heritability estimates of 60-80%. Genetic factors such as rare variants of TREM2 (triggering receptor expressed on myeloid cells-2) strongly increase the risk of developing AD, confirming the role of microglia in AD pathogenesis. In the last 5 years, several studies have dissected the mechanisms by which TREM2, as well as its rare variants affect amyloid and tau pathologies and their consequences in both animal models and in human studies. In this review, we summarize increases in our understanding of the involvement of TREM2 and microglia in AD development that may open new therapeutic strategies targeting the immune system to influence AD pathogenesis.

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Fig. 1 TREM2 ligands, signaling and functions. Ligands binding to TREM2 induce the association of TREM2 to DAP12 through an electrostatic interaction between a conserved positively-charged lysine in TREM2 (aa186) and a negatively- charged aspartic acid residue in DAP12, generating tyrosine phosphorylation of DAP12 within its immunoreceptor tyrosine-based activation motifs (ITAMS) by Src family kinasesCC BY · PubMed Central

Fig. 2 Schematic summary of the role of TREM2 and its variants in AD. a. Functional TREM2 has been suggested to allow microglia activation (by amyloid and NFTs for example), promote microglia clustering around plaques, amyloid uptake (early stage of the disease) and plaque compaction through binding to plaque-associated ApoE or directly to oligomeric Aβ. b. AD-associated TREM2 variants resulting in TREM2 partial loss-of-function abolished microglia clustering around plaque and phagocytic activity. These changes could be caused by a blockage of microglia in homeostatic stages because of less plaque-associated ApoE or other reasons. The consequences are filamentous plaques associate with increased dystrophic neurites and a possible increase of tau pathology (in early stages)CC BY · PubMed Central

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Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429
2016 Alzheimer's disease facts and figures
Alzheimer's Association (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.03.001 · Cited by 5,069
Inflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514
Intraneuronal β-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation
Oakley, H., Cole, S. L., Logan, S., Maus, E., Shao, P., Craft, J., Guillozet-Bongaarts, A., Ohno, M., Disterhoft, J., Van Eldik, L., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1202-06.2006 · Cited by 3,530
Neuropathological alterations in Alzheimer disease
Serrano-Pozo, A., Frosch, M. P., Masliah, E., & Hyman, B. T. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006189 · Cited by 3,345
TREM2 Variants in Alzheimer's Disease
Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211851 · Cited by 3,020
The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases
Krasemann, S., Madore, C., Cialic, R., Baufeld, C., Calcagno, N., El Fatimy, R., Beckers, L., O’Loughlin, E., Xu, Y., Fanek, Z., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.08.008 · Cited by 2,979
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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
Identification of a unique TGF-β–dependent molecular and functional signature in microglia
Butovsky, O., Jedrychowski, M. P., Moore, C. S., Cialic, R., Lanser, A. J., Gabriely, G., Koeglsperger, T., Dake, B., Wu, P. M., Doykan, C. E., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3599 · Cited by 2,543
Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.010 · Cited by 2,208

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Additional file 6 of Proteomic analysis across patient iPSC-based models and human post-mortem hippocampal tissue reveals early cellular dysfunction and progression of Alzheimer’s disease pathogenesis
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Additional file 5 of Proteomic analysis across patient iPSC-based models and human post-mortem hippocampal tissue reveals early cellular dysfunction and progression of Alzheimer’s disease pathogenesis
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Additional file 2 of Proteomic analysis across patient iPSC-based models and human post-mortem hippocampal tissue reveals early cellular dysfunction and progression of Alzheimer’s disease pathogenesis
Pomeshchik, Y., Velásquez, E., Gil, J., Klementieva, O. L., Gidlöf, R., Sydoff, M., Bagnoli, S., Nacmias, B., Sorbi, S., Westergren‐Thorsson, G., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24151166
Additional file 4 of Proteomic analysis across patient iPSC-based models and human post-mortem hippocampal tissue reveals early cellular dysfunction and progression of Alzheimer’s disease pathogenesis
Pomeshchik, Y., Velásquez, E., Gil, J., Klementieva, O. L., Gidlöf, R., Sydoff, M., Bagnoli, S., Nacmias, B., Sorbi, S., Westergren‐Thorsson, G., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24151172
Additional file 3 of Proteomic analysis across patient iPSC-based models and human post-mortem hippocampal tissue reveals early cellular dysfunction and progression of Alzheimer’s disease pathogenesis
Pomeshchik, Y., Velásquez, E., Gil, J., Klementieva, O. L., Gidlöf, R., Sydoff, M., Bagnoli, S., Nacmias, B., Sorbi, S., Westergren‐Thorsson, G., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24151169
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References
(2024) · Elsevier eBooks · doi:10.1016/b978-0-443-23565-8.09996-8
New Research on Biomarkers in Alzheimer’s Continuum
Vecchio, I., & Colica, C. (2025) · Reviews on Recent Clinical Trials · doi:10.2174/0115748871331138250114052615 · Cited by 2
Alzheimer’s Disease
Chan, D., Spires‐Jones, T. L., Provenzano, F. A., Glennon, E. B. C., & Duff, K. (2025) · Oxford University Press eBooks · doi:10.1093/med/9780190065324.003.0020
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Tereshchenko, S. Y., Potupchik, T. V., Evert, L. S., Alieva, L. G., Kozyrina, Y. E., & Maremkulov, A. A. (2025) · Molekulyarnaya Meditsina (Molecular medicine) · doi:10.29296/24999490-2025-01-02
Galectin-3 drives neuroinflammatory amyloid remodeling by stabilizing intermediate Aβ species and altering lysosomal processingPreprint
Camprubí-Ferrer, L., Soldán-Hidalgo, J., Axell, E., Dell’Eva, M., García-Cruzado, M., García‐Revilla, J., Yang, Y., Fernández‐Calle, R., Larlham, L., Chouhan, B., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.17.643790 · Cited by 1
Anti-Aβ immunotherapy-mediated amyloid clearance attenuates microglial activation without inducing exhaustion at residual plaquesPreprint
de Weerd, L., Hummel, S., Müller, S. A., Paris, I., Sandmann, T., Eichholtz, M., Gröger, R., Englert, A. L., Wagner, S., Ha, C., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.10.645950
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Yuan, S., Gaamouch, F. E., Cho, S., Kuncewicz, K., Nada, H., & Gabr, M. T. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.22.660908
The Microglial Trem2 R47H Alzheimer’s Disease Risk Variant Does Not Detectably Alter Hippocampal Synaptic Transmission in Young MicePreprint
Aljawder, A. I., Choudhury, H., Cummings, D. M., Wood, J. I., & Edwards, F. A. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.22.671714
Alzheimer’s Disease: Pathophysiological and Therapeutical Insights
Tyagi, K., Sarup, P., & Malik, J. (2025) · Nutritional neurosciences · doi:10.1007/978-981-95-2736-6_1 · Cited by 1
Additional file 1 of Multi-tissue neocortical transcriptome-wide association study implicates 8 genes across 6 genomic loci in Alzheimer’s disease
Gockley, J., Montgomery, K. S., Poehlman, W. L., Wiley, J. C., Liu, Y., Gerasimov, E. S., Greenwood, A. K., Sieberts, S. K., Wingo, A. P., Wingo, T. S., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14538753
Additional file 3 of Opposing effects of apoE2 and apoE4 on microglial activation and lipid metabolism in response to demyelination
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Additional file 4 of Opposing effects of apoE2 and apoE4 on microglial activation and lipid metabolism in response to demyelination
Wang, N., Wang, M., Jeevaratnam, S., Rosenberg, C. L., Ikezu, T. C., Shue, F., Doss, S. V., Alnobani, A., Martens, Y. A., Wren, M. C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21622304
Additional file 2 of TREM2 modulates differential deposition of modified and non-modified Aβ species in extracellular plaques and intraneuronal deposits
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Additional file 8 of Proteomic analysis across patient iPSC-based models and human post-mortem hippocampal tissue reveals early cellular dysfunction and progression of Alzheimer’s disease pathogenesis
Pomeshchik, Y., Velásquez, E., Gil, J., Klementieva, O. L., Gidlöf, R., Sydoff, M., Bagnoli, S., Nacmias, B., Sorbi, S., Westergren‐Thorsson, G., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24151190
Additional file 7 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
Jagadeesan, N., Roules, G. C., Chandrashekar, D. V., Yang, J., Kolluru, S., & Sumbria, R. K. (2024) · Figshare · doi:10.6084/m9.figshare.26694843
Additional file 1 of Higher CSF sTREM2 attenuates ApoE4-related risk for cognitive decline and neurodegeneration
Franzmeier, N., Suárez‐Calvet, M., Frontzkowski, L. K., Moore, A. M., Hohman, T. J., Morenas‐Rodríguez, E., Nuscher, B., Shaw, L. M. J., Trojanowski, J. Q., Dichgans, M., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13071124
Additional file 6 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
Jagadeesan, N., Roules, G. C., Chandrashekar, D. V., Yang, J., Kolluru, S., & Sumbria, R. K. (2024) · Figshare · doi:10.6084/m9.figshare.26694840
Additional file 1 of TREM2 splice isoforms generate soluble TREM2 species that disrupt long-term potentiation
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Additional file 1 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
Jagadeesan, N., Roules, G. C., Chandrashekar, D. V., Yang, J., Kolluru, S., & Sumbria, R. K. (2024) · Figshare · doi:10.6084/m9.figshare.26694825
Additional file 5 of Opposing effects of apoE2 and apoE4 on microglial activation and lipid metabolism in response to demyelination
Wang, N., Wang, M., Jeevaratnam, S., Rosenberg, C. L., Ikezu, T. C., Shue, F., Doss, S. V., Alnobani, A., Martens, Y. A., Wren, M. C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21622307
Additional file 6 of LILRB2-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) · Figshare · doi:10.6084/m9.figshare.20098700
Additional file 5 of LILRB2-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) · Figshare · doi:10.6084/m9.figshare.20098697
Additional file 9 of Proteomic analysis across patient iPSC-based models and human post-mortem hippocampal tissue reveals early cellular dysfunction and progression of Alzheimer’s disease pathogenesis
Pomeshchik, Y., Velásquez, E., Gil, J., Klementieva, O. L., Gidlöf, R., Sydoff, M., Bagnoli, S., Nacmias, B., Sorbi, S., Westergren‐Thorsson, G., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24151193
Additional file 3 of LILRB2-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) · Figshare · doi:10.6084/m9.figshare.20098691
Additional file 2 of LILRB2-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) · Figshare · doi:10.6084/m9.figshare.20098688
Additional file 1 of Proteomic analysis across patient iPSC-based models and human post-mortem hippocampal tissue reveals early cellular dysfunction and progression of Alzheimer’s disease pathogenesis
Pomeshchik, Y., Velásquez, E., Gil, J., Klementieva, O. L., Gidlöf, R., Sydoff, M., Bagnoli, S., Nacmias, B., Sorbi, S., Westergren‐Thorsson, G., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24151163
Additional file 4 of LILRB2-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) · Figshare · doi:10.6084/m9.figshare.20098694
Additional file 10 of LILRB2-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) · Figshare · doi:10.6084/m9.figshare.20098679
Additional file 1 of LILRB2-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) · Figshare · doi:10.6084/m9.figshare.20098685
Additional file 9 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
Jagadeesan, N., Roules, G. C., Chandrashekar, D. V., Yang, J., Kolluru, S., & Sumbria, R. K. (2024) · Figshare · doi:10.6084/m9.figshare.26694849
Additional file 13 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
Jagadeesan, N., Roules, G. C., Chandrashekar, D. V., Yang, J., Kolluru, S., & Sumbria, R. K. (2024) · Figshare · doi:10.6084/m9.figshare.26694861
Additional file 1 of Effects of microglial depletion and TREM2 deficiency on Aβ plaque burden and neuritic plaque tau pathology in 5XFAD mice
Delizannis, A. T., Nonneman, A., Tsering, W., Bondt, A. D., den Wyngaert, I. V., Zhang, B., Meymand, E. S., Olufemi, M. F., Koivula, P. P., Maimaiti, S., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16599810
Additional file 8 of LILRB2-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) · Figshare · doi:10.6084/m9.figshare.20098706
Additional file 5 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
Jagadeesan, N., Roules, G. C., Chandrashekar, D. V., Yang, J., Kolluru, S., & Sumbria, R. K. (2024) · Figshare · doi:10.6084/m9.figshare.26694837
Additional file 7 of LILRB2-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) · Figshare · doi:10.6084/m9.figshare.20098703
Additional file 4 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
Jagadeesan, N., Roules, G. C., Chandrashekar, D. V., Yang, J., Kolluru, S., & Sumbria, R. K. (2024) · Figshare · doi:10.6084/m9.figshare.26694834
Additional file 7 of Proteomic analysis across patient iPSC-based models and human post-mortem hippocampal tissue reveals early cellular dysfunction and progression of Alzheimer’s disease pathogenesis
Pomeshchik, Y., Velásquez, E., Gil, J., Klementieva, O. L., Gidlöf, R., Sydoff, M., Bagnoli, S., Nacmias, B., Sorbi, S., Westergren‐Thorsson, G., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24151187
Additional file 8 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
Jagadeesan, N., Roules, G. C., Chandrashekar, D. V., Yang, J., Kolluru, S., & Sumbria, R. K. (2024) · Figshare · doi:10.6084/m9.figshare.26694846
Additional file 6 of Opposing effects of apoE2 and apoE4 on microglial activation and lipid metabolism in response to demyelination
Wang, N., Wang, M., Jeevaratnam, S., Rosenberg, C. L., Ikezu, T. C., Shue, F., Doss, S. V., Alnobani, A., Martens, Y. A., Wren, M. C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21622310
Additional file 12 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
Jagadeesan, N., Roules, G. C., Chandrashekar, D. V., Yang, J., Kolluru, S., & Sumbria, R. K. (2024) · Figshare · doi:10.6084/m9.figshare.26694858
Additional file 10 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
Jagadeesan, N., Roules, G. C., Chandrashekar, D. V., Yang, J., Kolluru, S., & Sumbria, R. K. (2024) · Figshare · doi:10.6084/m9.figshare.26694852
Additional file 2 of Opposing effects of apoE2 and apoE4 on microglial activation and lipid metabolism in response to demyelination
Wang, N., Wang, M., Jeevaratnam, S., Rosenberg, C. L., Ikezu, T. C., Shue, F., Doss, S. V., Alnobani, A., Martens, Y. A., Wren, M. C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21622298
Additional file 1 of Opposing effects of apoE2 and apoE4 on microglial activation and lipid metabolism in response to demyelination
Wang, N., Wang, M., Jeevaratnam, S., Rosenberg, C. L., Ikezu, T. C., Shue, F., Doss, S. V., Alnobani, A., Martens, Y. A., Wren, M. C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21622295
Additional file 3 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
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Additional file 1 of TREM2 modulates differential deposition of modified and non-modified Aβ species in extracellular plaques and intraneuronal deposits
Joshi, P., Riffel, F., Kumar, S., Villacampa, N., Theil, S., Parhizkar, S., Haass, C., Colonna, M., Heneka, M. T., Arzberger, T., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16829555
Additional file 9 of LILRB2-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) · Figshare · doi:10.6084/m9.figshare.20098712
Additional file 2 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
Jagadeesan, N., Roules, G. C., Chandrashekar, D. V., Yang, J., Kolluru, S., & Sumbria, R. K. (2024) · Figshare · doi:10.6084/m9.figshare.26694828
Additional file 1 of Astrocyte-specific knockout of YKL-40/Chi3l1 reduces Aβ burden and restores memory functions in 5xFAD mice
Zeng, X., Cheung, S. K. K., Shi, M., Or, P. M. Y., Li, Z., Liu, J. Y. H., Ho, W. L.-H., Liu, T., Lu, K., Rudd, J. A., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26648808
Additional file 11 of LILRB2-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) · Figshare · doi:10.6084/m9.figshare.20098682
Additional file 11 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
Jagadeesan, N., Roules, G. C., Chandrashekar, D. V., Yang, J., Kolluru, S., & Sumbria, R. K. (2024) · Figshare · doi:10.6084/m9.figshare.26694855
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Kesisoglou, E. (2020) · theses.fr (ABES) · doi:10.70675/691831c4z5491z4cb9zb88az10456e67b7ce
Recherches de biomarqueurs impliqués dans la maladie d’Alzheimer et associés à la protéine DYRK1A dans le syndrome de Down pour valider des traitements potentiels
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Pou, M. L. (2023) · theses.fr (ABES) · doi:10.70675/0424309azddeaz4545z8176z8df20cea5e8f
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Bauer, C. (2023) · theses.fr (ABES) · doi:10.70675/0d82043ezd7c7z4fb4z9fc8ze2d05d18b02b
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Nema, S., Sharma, A., Werneburg, S., Singh, A., & Singh, Y. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-33623-2.00014-3
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Hossain, M. M., Adhikari, J., Fardous, J., Ahmed, S., Ferdous, M. T., & Shibly, A. Z. (2026) · Next research. · doi:10.1016/j.nexres.2026.102314
Human Stem Cell-Derived Models of the Alzheimer’s Disease Neuroimmune System
Summers, R., Quang, D., & Johnson, N. R. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27167360 · Cited by 1
Research Progress on the Pathogenesis of Alzheimer’s Disease and the Advancement of Characteristic Acupuncture Therapy
潘, 炫. (2026) · Journal of Clinical Personalized Medicine · doi:10.12677/jcpm.2026.54258
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Chmielewski, P. P. (2026) · Cells · doi:10.3390/cells15171599
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Procopciuc, L. M., Hangan, A. C., Gog-Bogdan, S., & Lucaciu, R. L. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27188122 · Cited by 1
XL-MS and De Novo Protein Design Identified a Common Motif for TREM2 Binding
Perera, D., Ajiboye, E. G., Pitakatuwana, K., Wier, S., Duong, V., & Wu, H. (2026) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.6c00310
Repeated clinical trial failures in Alzheimer’s disease: The pitfalls of pursuing epidemiological associations
Imbimbo, B. P., Pomara, N., Pini, L., & Frederiksen, K. S. (2026) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2026.119943
Activation of TREM2 via single-domain antibodies improves synaptic and cognitive function in 5×FAD mice
Yu, X., Ren, Q., Gao, Y., Xie, S., Dang, R., Meng, J., Su, Z., Li, M., Ao, Y., Liu, A., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.118063
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Seol, S.-I., Kim, J., Davaanyam, D., Park, S., Lee, E.-H., Han, P.-L., Kim, T.-K., & Lee, J.-K. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27198681
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Martin, E., & Versées, W. (2026) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2026.2743893
BindingDB Entry 50012896: Quinoline-Pyrazole Scaffold as a Novel Ligand of Galectin-3 and Suppressor of TREM2 Signaling.
BindingDB (2022) · UC San Diego · doi:10.7270/q29w0k63
Supplementary data & code for "Early intervention anti-Aβ immunotherapy attenuates microglial activation without inducing exhaustion at residual plaques"
Sandmann, T. (2025) · Zenodo (CERN European Organization for Nuclear Research) · doi:10.5281/zenodo.14812454

Authors: Gratuze, M., Leyns, C. E. G., & Holtzman, D. M.
Affiliations: Washington University in St. Louis (US)
Corresponding author: Holtzman, David M.
ORCID: Gratuze, Maud
Leyns, Cheryl E. G.
Holtzman, David M.
Venue: Molecular Neurodegeneration
Publisher: Springer Science and Business Media LLC
Published: 2018-12
Volume: 13
Issue: 1
Pages: 66-66
ISSN: 1750-1326 (ISSN-L)
DOI: 10.1186/s13024-018-0298-9
PMC: PMC6302500
OpenAlex: W2905219483
Cited by: 489
References: 166
Citations by year: 2026: 40 · 2025: 59 · 2024: 83 · 2023: 63 · 2022: 84 · 2021: 86 · 2020: 52 · 2019: 22
FWCI: 3.80
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (tdm)
Locations: Molecular Neurodegeneration (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, other-oa)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by)
HAL (submittedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders: Edward N. and Della L. Thome Memorial Foundation (none)
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, microglia, amyloid plaques, amyloid-beta, tau pathology, genetic risk variants, late-onset Alzheimer's disease, neuroinflammation, therapeutic target, immune system
MeSH terms: Alzheimer Disease, Animals, Disease Models, Animal, Humans, Membrane Glycoproteins, Receptors, Immunologic, Amyloid beta-Peptides, Microglia, Plaque, Amyloid

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

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