The most prevalent rare coding variants of TREM2 conferring risk of Alzheimer's disease: A systematic review and meta‑analysis

Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses

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<i>TREM2</i> Variants in Alzheimer's Disease

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Variant of <i>TREM2</i> Associated with the Risk of Alzheimer's Disease

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TREM2 Lipid Sensing Sustains the Microglial Response in an Alzheimer’s Disease Model

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Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

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TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia

Yeh, F. L., Wang, Y., Tom, I., Gonzalez, L. C., & Sheng, M. (2016) · Neuron · doi:10.1016/j.neuron.2016.06.015 · Cited by 943 · see citing works

TREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy

Yuan, P., Condello, C., Keene, C. D., Wang, Y., Bird, T. D., Paul, S. M., Luo, W., Colonna, M., Baddeley, D., & Grutzendler, J. (2016) · Neuron · doi:10.1016/j.neuron.2016.05.003 · Cited by 817 · see citing works

Mutations in Two Genes Encoding Different Subunits of a Receptor Signaling Complex Result in an Identical Disease Phenotype

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Alzheimer Disease

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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 · see citing works

TREM2 in neurodegeneration: evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson’s disease

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Coding variants in TREM2 increase risk for Alzheimer's disease

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The Triggering Receptor Expressed on Myeloid Cells 2 Binds Apolipoprotein E

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

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

<i>TREM2</i>Variant p.R47H as a Risk Factor for Sporadic Amyotrophic Lateral Sclerosis

Cady, J., Koval, E. D., Benitez, B. A., Zaidman, C., Jockel-Balsarotti, J., Allred, P., Baloh, R. H., Ravits, J., Simpson, E., Appel, S. H., et al. (2014) · JAMA Neurology · doi:10.1001/jamaneurol.2013.6237 · Cited by 262 · see citing works

An Alzheimer‐associated TREM2 variant occurs at the ADAM cleavage site and affects shedding and phagocytic function

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TREM2and Neurodegenerative Disease

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The Trem2 R47H variant confers loss-of-function-like phenotypes in Alzheimer's disease

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Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms

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TREM2 haplodeficiency in mice and humans impairs the microglia barrier function leading to decreased amyloid compaction and severe axonal dystrophy

Yuan, P., Condello, C., Keene, C. D., Wang, Y., Bird, T. D., Paul, S. M., Luo, W., Colonna, M., Baddeley, D., & Grutzendler, J. (2016) · Neuron · doi:10.1016/j.neuron.2016.09.016 · Cited by 219 · see citing works

Investigating the role of rare heterozygous TREM2 variants in Alzheimer's disease and frontotemporal dementia.

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Genomic variants, genes, and pathways of Alzheimer's disease: An overview

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The Trem2 R47H Alzheimer's risk variant impairs splicing and reduces Trem2 mRNA and protein in mice but not in humans

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Contribution to Alzheimer's disease risk of rare variants in TREM2, SORL1, and ABCA7 in 1779 cases and 1273 controls

Bellenguez, C., Charbonnier, C., Grenier-Boley, B., Quenez, O., Le Guennec, K., Nicolas, G., Chauhan, G., Wallon, D., Rousseau, S., Richard, A. C., et al. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.07.001 · Cited by 166 · see citing works

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

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TREM2 R47H Variant as a Risk Factor for Early-Onset Alzheimer's Disease

Pottier, C. P., collaborators, G., Wallon, D., Rousseau, S., Rovelet‐Lecrux, A., Richard, A., Rollin‐Sillaire, A., Frébourg, T., Campion, D., & Hannequin, D. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-122311 · Cited by 162 · see citing works

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

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

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

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

Variants in triggering receptor expressed on myeloid cells 2 are associated with both behavioral variant frontotemporal lobar degeneration and Alzheimer's disease

Giraldo, M., Lopera, F., Siniard, A. L., Corneveaux, J. J., Schrauwen, I., Carvajal, J., Muñoz, C., Ramirez-Restrepo, M., Gaiteri, C., Myers, A. J., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.02.016 · Cited by 147 · see citing works

TREM2-activating antibodies abrogate the negative pleiotropic effects of the Alzheimer's disease variant Trem2R47H on murine myeloid cell function

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 · see citing works

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

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Assessing the role of the TREM2 p.R47H variant as a risk factor for Alzheimer's disease and frontotemporal dementia

Ruiz, A., Dols-Icardo, O., Bullido, M. J., Pastor, P., Rodríguez-Rodríguez, E., López de Munain, A., de Pancorbo, M. M., Pérez-Tur, J., Álvarez, V., Antonell, A., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.08.011 · Cited by 118 · see citing works

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

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

The triggering receptor expressed on myeloid cells 2 ( <i>TREM2</i> ) is associated with enhanced inflammation, neuropathological lesions and increased risk for Alzheimer's dementia

Roussos, P., Katsel, P., Fam, P., Tan, W., Purohit, D. P., & Haroutunian, V. (2015) · Alzheimer's &amp; Dementia · doi:10.1016/j.jalz.2014.10.013 · Cited by 103 · see citing works

A novel mutation in TREM2 gene causing Nasu-Hakola disease and review of the literature

Dardiotis, E., Siokas, V., Pantazi, E., Dardioti, M., Rikos, D., Xiromerisiou, G., Markou, A., Papadimitriou, D. A., Speletas, M. G., & Hadjigeorgiou, G. M. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.01.015 · Cited by 89 · see citing works

Lack of Genetic Association Between <i>TREM2</i> and Late-Onset Alzheimer's Disease in a Japanese Population

Miyashita, A., Wen, Y., Kitamura, N., Matsubara, E., Kawarabayashi, T., Shoji, M., Tomita, N., Furukawa, K., Arai, H., Asada, T., et al. (2014) · Journal of Alzheimer’s Disease · doi:10.3233/jad-140225 · Cited by 69 · see citing works

Triggering receptor expressed on myeloid cells 2 variant is rare in late-onset Alzheimer's disease in Han Chinese individuals

Yu, J.-T., Jiang, T., Wang, Y.-L., Wang, H.-F., Zhang, W., Hu, N., Tan, L., Sun, L., Tan, M.-S., Zhu, X.-C., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.10.075 · Cited by 68 · see citing works

Investigation of TREM2, PLD3, and UNC5C variants in patients with Alzheimer's disease from mainland China

Jiao, B., Liu, X., Tang, B., Hou, L., Zhou, L., Zhang, F., Zhou, Y., Guo, J., Yan, X., & Shen, L. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.04.025 · Cited by 66 · see citing works

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

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

Assessment of TREM2 rs75932628 association with Alzheimer's disease in a population-based sample: the Cache County Study

Murcia, J. D. G., Schmutz, C., Munger, C., Perkes, A. D., Gustin, A. J., Peterson, M., Ebbert, M., Norton, M. C., Tschanz, J. T., Munger, R. G., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.06.004 · Cited by 54 · see citing works

More evidence for association of a rare TREM2 mutation (R47H) with Alzheimer's disease risk

Rosenthal, S. L., Bamne, M. N., Wang, X., Berman, S., Snitz, B. E., Klunk, W. E., Sweet, R. A., Demirci, F. Y., López, O. L., & Kamboh, M. I. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.04.012 · Cited by 53 · see citing works

Transethnic meta-analysis of rare coding variants in PLCG2, ABI3, and TREM2 supports their general contribution to Alzheimer’s disease

Dalmasso, M. C., Brusco, L. I., Olivar, N., Muchnik, C., Hanses, C., Milz, E., Becker, J., Heilmann-Heimbach, S., Hoffmann, P., Prestia, F. A., et al. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0394-9 · Cited by 51 · see citing works

The Triggering Receptor Expressed on Myeloid Cells 2: “TREM-ming” the Inflammatory Component Associated with Alzheimer's Disease

Rohn, T. T. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/860959 · Cited by 48 · see citing works

Mutation analysis of patients with neurodegenerative disorders using NeuroX array

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TREM2 analysis and increased risk of Alzheimer's disease

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Mutation analysis of the MS4A and TREM gene clusters in a case-control Alzheimer's disease data set

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Association study ofTREM2polymorphism rs75932628 with late-onset Alzheimer’s disease in Chinese Han population

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Association of Variants in PINX1 and TREM2 With Late-Onset Alzheimer Disease

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Exome array study did not identify novel variants in Alzheimer's disease

Chung, S. J., Kim, M., Kim, J., Kim, Y. J., You, S., Koh, J., Kim, S. Y., & Lee, J. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.03.007 · Cited by 25 · see citing works

Association Study of the TREM2 Gene and Identification of a Novel Variant in Exon 2 in Iranian Patients with Late-Onset Alzheimer's Disease

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Lack of association between triggering receptor expressed on myeloid cells 2 polymorphism rs75932628 and late-onset Alzheimer’s disease in a Chinese Han population

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TREM2 variants in neurodegenerative disorders in the Polish population. Homozygosity and compound heterozygosity in FTD patients

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

The p.R47H Variant of TREM2 Gene is Associated With Late-onset Alzheimer Disease in Colombian Population

Bustos, C., Ortega-Rojas, J., Mahecha, M. F., Arboleda, G., Vásquez, R., Pardo, R., & Arboleda, H. (2018) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000275 · Cited by 10 · see citing works

Frequency of the TREM2 R47H Variant in Various Neurodegenerative Disorders

Ayer, A. H., Wojta, K. J., Ramos, E. M., Dokuru, D. R., Chen, J., Karydas, A. M., Papatriantafyllou, J. D., Agiomyrgiannakis, D., Kamtsadeli, V., Tsinia, N., et al. (2019) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000339 · Cited by 9 · see citing works

Genetic Analysis of TREM2 Variants in Tunisian Patients with Alzheimer's Disease

Landoulsi, Z., Djebara, M. B., Kacem, I., Sidhom, Y., Kéfi, R., Abdelhak, S., Gargouri, A., & Gouider, R. (2018) · Medical Principles and Practice · doi:10.1159/000489779 · Cited by 8 · see citing works

Role of neuroinflammation in neurodegeneration development

Zhang, W., Xiao, D., Mao, Q., & Xia, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01486-5 · Cited by 1,668 · see citing works

Genomics of Alzheimer’s disease implicates the innate and adaptive immune systems

Li, Y., Laws, S. M., Miles, L. A., Wiley, J. S., Huang, X., Masters, C. L., & Gu, B. J. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03986-5 · Cited by 93 · see citing works

Effect of neuroinflammation on the progression of Alzheimer’s disease and its significant ramifications for novel anti-inflammatory treatments

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Tracking neuroinflammatory biomarkers in Alzheimer’s disease: a strategy for individualized therapeutic approaches?

Lista, S., Imbimbo, B. P., Grasso, M., Fidilio, A., Emanuele, E., Minoretti, P., López-Ortiz, S., Martín-Hernández, J., Gabelle, A., Caruso, G., et al. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03163-y · Cited by 81 · see citing works

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

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

APOE and immunity: Research highlights

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Intracellular accumulation of amyloid-ß is a marker of selective neuronal vulnerability in Alzheimer’s disease

Caramello, A., Fancy, N. N., Tournerie, C., Eklund, M., Chau, V. M. N., Adair, E., Papageorgopoulou, M., Willumsen, N., Jackson, J., Hardy, J., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-60328-w · Cited by 37 · see citing works

TREM2 risk variants are associated with atypical Alzheimer’s disease

Kim, B., Suh, E. R., Nguyen, A. T., Prokop, S., Mikytuck, B., Olatunji, O. A., Robinson, J. L., Grossman, M., Phillips, J. S., Irwin, D. J., et al. (2022) · Acta Neuropathologica · doi:10.1007/s00401-022-02495-4 · Cited by 29 · see citing works

Contribution of CNS and extra-CNS infections to neurodegeneration: a narrative review

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Key variants via the Alzheimer's Disease Sequencing Project whole genome sequence data

Wang, Y., Sarnowski, C., Lin, H., Pitsillides, A., Heard‐Costa, N. L., Choi, S. H., Wang, D., Bis, J. C., Blue, E., (ADNI), T. A. D. N. I., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13705 · Cited by 24 · see citing works

TREM2 in Neurodegenerative Disorders: Mutation Spectrum, Pathophysiology, and Therapeutic Targeting

Yang, H.-W., Kim, D., Yang, Y., Bagyinszky, E., & An, S. S. A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26157057 · Cited by 25 · see citing works

Current understanding on TREM-2 molecular biology and physiopathological functions

Bharadwaj, S., Groza, Y., Mierzwicka, J. M., & Malý, P. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.112042 · Cited by 22 · see citing works

The Hidden Role of Non-Canonical Amyloid β Isoforms in Alzheimer’s Disease

Busch, L., Eggert, S., Endres, K., & Bufe, B. (2022) · Cells · doi:10.3390/cells11213421 · Cited by 19 · see citing works

Dynamic insights into the effects of nonsynonymous polymorphisms (nsSNPs) on loss of TREM2 function

Dash, R., Munni, Y. A., Mitra, S., Choi, H. J., Jahan, S. I., Chowdhury, A., Jang, T. J., & Moon, I. S. (2022) · Scientific Reports · doi:10.1038/s41598-022-13120-5 · Cited by 18 · see citing works

Alternative Splicing Regulation of Low-Frequency Genetic Variants in Exon 2 of TREM2 in Alzheimer’s Disease by Splicing-Based Aggregation

Han, S., Na, Y., Koh, I., Nho, K. T., & Lee, Y. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22189865 · Cited by 16 · see citing works

Emerging roles for ITAM and ITIM receptor signaling in microglial biology and Alzheimer's disease‐related amyloidosis

Samuels, J. D., Lukens, J. R., & Price, R. J. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15981 · Cited by 13 · see citing works

Therapeutic Targets in Innate Immunity to Tackle Alzheimer’s Disease

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The synergistic interplay between vitamin A, dietary fiber, and the microbiota-gut-brain axis: a potential mechanism for preventing Alzheimer’s disease

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Biologics as Therapeutical Agents Under Perspective Clinical Studies for Alzheimer’s Disease

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The role of triggering receptor expressed on myeloid cells 2 in Parkinson’s disease and other neurodegenerative disorders

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Mechanisms of increased Alzheimer’s disease pathology with R47H and R62H TREM2 variants

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Thyroid Hormone and Alzheimer Disease: Bridging Epidemiology to Mechanism

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Dissecting the immune response of CD4+ T cells in Alzheimer’s disease

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The genetic risk factors, molecular pathways, microRNAs, and the gut microbiome in Alzheimer’s disease

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Towards a structural and functional analysis of the immunoglobulin-fold proteome

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TREM2 coding variants in Slovak Alzheimer's disease patients

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Biophysical characterization of TREM2 missense variants implicated in neurodegenerative disease

Pillai, J. P., Sung, K., Shi, L. Z., & Wu, C. (2025) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2025.07.003 · Cited by 2 · see citing works

The TREM2 paradox in fibrosis: a unified mechanism for opposite outcomes across organs

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Co-occurring pathogenic variants in 6q27 associated with dementia spectrum disorders in a Peruvian family

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TREM2 Gene Compound Heterozygosity in Neurodegenerative Disorders

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APOE, Inflammation, and T Cells in Translational Disease Models and Clinical Medicine

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Evaluating the pathogenicity, stability, and stereochemical effects of variants of unknown significance in TREM2 using orthogonal structural analysesPreprint

Pillai, J. P., Sung, K., Shi, L. Z., & Wu, C. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.25.656054

A Randomized Controlled Trial: The Effect of Breast Milk Odor on Bilirubin Levels and Duration of Phototherapy in Babies Receiving Phototherapy

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APOE, Inflammation, and T Cells in Translational Disease Models and Clinical Medicine

Adlimoghaddam, A., Cervantes, D., & Wheeler, C. J. (2026) · Springer eBooks · doi:10.1007/978-3-031-52641-1_35-1

Développement d’un test sanguin pour le dépistage de la maladie d’Alzheimer

Torres, F. D. (2022) · doi:10.70675/afbb97a5z1636z46abz844czb340616aeda1

Hétérogénéité et régulation des astrocytes dans la maladie d'Alzheimer : vers des interventions ciblées sur les voies JAK2-STAT3 et NF-kB

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Enhancing global Alzheimer's disease drug outcomes by comprehensive African data integration

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Polygenic Risk Scores in Alzheimer’s Disease: A Cross-Scale View from Genes to Brain and Behavior

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Sex chromosome and gonadal regulation of cardiac myofibroblast activation decoupled using mechanically tunable hydrogels and the Four Core Genotypes modelPreprint

Gorashi, R. M., Baddour, T., Richter, K., Nguyen, A. K., Faust, M. N., Loud, M. C., Broders, S. L., Zheng, Q., Graner, L., Chen, X., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.13.758988

A rare coding variant in TREM2 increases risk for Alzheimer’s disease in Han Chinese (P5.164)

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

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The rare TREM2 R47H variant exerts only a modest effect on Alzheimer disease risk

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TREM2 variants and risk of Alzheimer’s disease: a meta-analysis

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Investigating the role of rare heterozygous TREM2 variants in Alzheimer's disease and frontotemporal dementia.

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