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The triggering receptor expressed on myeloid cells 2 ( TREM2 ) is associated with enhanced inflammation, neuropathological lesions and increased risk for Alzheimer's dementia
Open accessAbstract
Introduction: The objective of this study was to elucidate the relationship between the triggering receptor expressed on myeloid cells 2 ( TREM2 ) risk variant, neuropathological lesions, alterations in gene and protein expression, and the severity of neuroinflammation. Methods: The genetic association study of the R47 H TREM2 variant with Alzheimer's disease (AD), neuropathology, and changes in TREM2 and TYRO protein tyrosine kinase‐binding protein ( TYROBP) gene and protein expression, and neuroinflammatory markers. Results: The TREM2 variant is associated with: (i) AD (odds ratio: 4.76; P = .014); (ii) increased density of amyloid plaques and neurofibrillary tangles in multiple brain regions; (iii) increased TREM2 ( P = .041) and TYROBP ( P = .006) gene expression; (iv) decreased TREM2 protein levels ( P = .016); and (v) upregulation of proinflammatory cytokines (regulated on activation, normal T cell expressed and secreted [RANTES] and interferon [IFN] gamma) ( P = .003) and nominal downregulation of protective markers (α2‐macroglobulin, interleukin 4 or IL‐4, and ApoA1) ( P = .018). Discussion: These findings link the TREM2 missense mutation with specific molecular abnormalities and increases in neuropathological lesions in the human brain.
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“They also reported higher TREM2 gene expression in AD R47H carriers relative to controls and no difference in TREM2 between AD noncarriers and control.”
From Markers of microglia in post-mortem brain samples from patients with Alzheimer’s disease: a systematic review (2018) · cites this paper as [107]
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“Their protein measurements, however, indicated decreased TREM2 in AD R47H carriers relative to controls with no difference between AD noncarriers and control.”
From Markers of microglia in post-mortem brain samples from patients with Alzheimer’s disease: a systematic review (2018) · cites this paper as [107]
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“Several other TREM2 variants that affect the expression of TREM2 also increased the risk of AD, including R62H, T66M, H157Y, and D87N.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [165]
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Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123
The Clinical Dementia Rating (CDR): Current version and scoring rules
Morris, J. C. (1993) · Neurology · doi:10.1212/wnl.43.11.2412-a · Cited by 9,882
Origin and physiological roles of inflammation
Medzhitov, R. (2008) · Nature · doi:10.1038/nature07201 · Cited by 6,618
Mirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., Belle, G. V., Berg, L., et al. (1991) · Neurology · doi:10.1212/wnl.41.4.479 · Cited by 4,961
Insights into the regulation of protein abundance from proteomic and transcriptomic analyses
Vogel, C., & Marcotte, E. M. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3185 · Cited by 4,195
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
Consortium to Establish a Registry for Alzheimer's Disease (CERAD)
Fillenbaum, G., & Heyman, A. (2002) · doi:10.1002/0470846410.ch42(iii · Cited by 2,859
Variant of TREM2 Associated with the Risk of Alzheimer's Disease
Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211103 · Cited by 2,558
A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline
Jonsson, T., Atwal, J. K., Steinberg, S., Snaedal, J., Jonsson, P. V., Bjornsson, S., Stefansson, H., Sulem, P., Gudbjartsson, D., Maloney, J., et al. (2012) · Nature · doi:10.1038/nature11283 · Cited by 1,738
Integrated Systems Approach Identifies Genetic Nodes and Networks in Late-Onset Alzheimer’s Disease
Zhang, B., Gaiteri, C., Bodea, L.-G., Wang, Z., McElwee, J., Podtelezhnikov, A. A., Zhang, C., Xie, T., Tran, L., Dobrin, R., et al. (2013) · Cell · doi:10.1016/j.cell.2013.03.030 · Cited by 1,657
Takahashi, K., Rochford, C. D. P., & Neumann, H. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041611 · Cited by 1,124
Blalock, E. M., Geddes, J. W., Chen, K. C., Porter, N. M., Markesbery, W. R., & Landfield, P. W. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308512100 · Cited by 1,025
Inflammation in Alzheimer Disease--A Brief Review of the Basic Science and Clinical Literature
Wyss-Coray, T., & Rogers, J. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006346 · Cited by 975
Microglia: Scapegoat, saboteur, or something else?
Aguzzi, A., Barres, B. A., & Bennett, M. L. (2013) · Science · doi:10.1126/science.1227901 · Cited by 836
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
Cutting Edge: TREM-2 Attenuates Macrophage Activation
Turnbull, I. R., Gilfillan, S., Cella, M., Aoshi, T., Miller, M., Piccio, L., Hernandez, M., & Colonna, M. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.6.3520 · Cited by 688
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
Cholinergic Markers in Elderly Patients With Early Signs of Alzheimer Disease
Davis, K. L. (1999) · JAMA · doi:10.1001/jama.281.15.1401 · Cited by 496
A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells by microglia
Hsieh, C. L., Koike, M., Spusta, S. C., Niemi, E. C., Yenari, M., Nakamura, M. C., & Seaman, W. E. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06042.x · Cited by 475
Hamerman, J. A., Jarjoura, J. R., Humphrey, M. B., Nakamura, M. C., Seaman, W. E., & Lanier, L. L. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.4.2051 · Cited by 440
Inflammatory process in Alzheimer's Disease
Meraz-Ríos, M. A., Toral-Rios, D., Franco-Bocanegra, D., Villeda-Hernández, J., & Campos-Peña, V. (2013) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2013.00059 · Cited by 427
Rayaprolu, S., Mullen, B., Baker, M., Lynch, T., Finger, E., Seeley, W. W., Hatanpaa, K. J., Lomen-Hoerth, C., Kertesz, A., Bigio, E. H., et al. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-19 · Cited by 404
GWAS of Cerebrospinal Fluid Tau Levels Identifies Risk Variants for Alzheimer’s Disease
Cruchaga, C., Kauwe, J. S. K., Harari, O., Jin, S. C., Cai, Y., Karch, C. M., Benitez, B. A., Jeng, A. T., Skorupa, T., Carrell, D., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.02.026 · Cited by 383
Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12
Hamerman, J. A., Tchao, N. K., Lowell, C. A., & Lanier, L. L. (2005) · Nature Immunology · doi:10.1038/ni1204 · Cited by 325
Haroutunian, V. (1998) · Archives of Neurology · doi:10.1001/archneur.55.9.1185 · Cited by 289
Self-citationTREM2and Neurodegenerative Disease
Reitz, C., & Mayeux, R. P. (2013) · New England Journal of Medicine · doi:10.1056/nejmc1306509 · Cited by 258
TREM2 is upregulated in amyloid plaque-associated microglia in aged APP23 transgenic mice
Frank, S., Burbach, G. J., Bonin, M., Walter, M., Streit, W., Bechmann, I., & Deller, T. (2008) · Glia · doi:10.1002/glia.20710 · Cited by 247
Inflammatory changes parallel the early stages of Alzheimer disease
Parachikova, A., Agadjanyan, M. G., Cribbs, D. H., Blurton-Jones, M., Perreau, V., Rogers, J., Beach, T. G., & Cotman, C. W. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.08.014 · Cited by 203
Neurofibrillary tangles in nondemented elderly subjects and mild Alzheimer disease
Haroutunian, V., Purohit, D. P., Perl, D. P., Marin, D., Khan, K., Lantz, M., Davis, K. L., & Mohs, R. C. (1999) · Archives of Neurology · doi:10.1001/archneur.56.6.713 · Cited by 201
Self-citationCuyvers, E., Bettens, K., Philtjens, S., Langenhove, T. V., Gijselinck, I., van der Zee, J., Engelborghs, S., Vandenbulcke, M., Dongen, J. V., Geerts, N., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.09.009 · Cited by 185
Ito, H., & Hamerman, J. A. (2012) · European Journal of Immunology · doi:10.1002/eji.201141679 · Cited by 173
Heterozygous TREM2 mutations in frontotemporal dementia
Borroni, B., Ferrari, F., Galimberti, D., Nacmias, B., Barone, C., Bagnoli, S., Fenoglio, C., Piaceri, I., Archetti, S., Bonvicini, C., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.09.017 · Cited by 173
Sessa, G., Podini, P., Mariani, M., Meroni, A., Spreafico, R., Sinigaglia, F., Colonna, M., Panina, P., & Meldolesi, J. (2004) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03729.x · Cited by 165
TREM2 is associated with the risk of Alzheimer's disease in Spanish population
Benitez, B. A., Cooper, B., Pastor, P., Jin, S.-C., Lorenzo, E., Cervantes, S., & Cruchaga, C. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.12.018 · Cited by 163
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
Melchior, B., Garcia, A., Hsiung, B., Lo, K. M., Doose, J. M., Thrash, J. C., Stalder, A. K., Staufenbiel, M., Neumann, H., & Carson, M. J. (2010) · ASN NEURO · doi:10.1042/an20100010 · Cited by 134
Sieber, M. W., Jaenisch, N., Brehm, M., Guenther, M., Linnartz‐Gerlach, B., Neumann, H., Witte, O. W., & Frahm, C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0052982 · Cited by 128
Jiang, T., Yu, J., Zhu, X., & Tan, L. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8424-8 · Cited by 122
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
Transcriptional vulnerability of brain regions in Alzheimer's disease and dementia
Haroutunian, V. H., Katsel, P., & Schmeidler, J. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.07.021 · Cited by 113
Self-citationMolecular and genetic evidence for abnormalities in the nodes of Ranvier in schizophrenia
Roussos, P. (2012) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.110 · Cited by 93
Self-citationA System-Level Transcriptomic Analysis of Schizophrenia Using Postmortem Brain Tissue Samples
Roussos, P., Katsel, P., Davis, K. L., Siever, L. J., & Haroutunian, V. (2012) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2012.704 · Cited by 92
Self-citationThe Clinical Dementia Rating scale
Dooneief, G., Marder, K. S., Tang, M., & Stern, Y. (1996) · Neurology · doi:10.1212/wnl.46.6.1746 · Cited by 86
Convergent Findings for Abnormalities of the NF-κB Signaling Pathway in Schizophrenia
Roussos, P., Katsel, P., Davis, K. L., Giakoumaki, S. G., Siever, L. J., Bitsios, P., & Haroutunian, V. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.215 · Cited by 69
Self-citationGain in Brain Immunity in the Oldest-Old Differentiates Cognitively Normal from Demented Individuals
Katsel, P., Tan, W., & Haroutunian, V. H. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007642 · Cited by 57
Self-citationMurcia, 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 55
Evidence of Trem2 Variant Associated with Triple Risk of Alzheimer’s Disease
Abduljaleel, Z., Al-Allaf, F. A., Khan, W., Athar, M., Shahzad, N., Taher, M. M., Elrobh, M., Alanazi, M. S., & El-Huneidi, W. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092648 · Cited by 54
TREM2 Risk Variant and Loss of Brain Tissue
Rajagopalan, P., Hibar, D. P., & Thompson, P. M. (2013) · Europe PMC (PubMed Central) · doi:10.1056/nejmc1306509#sa3 · Cited by 41
Alzheimer's disease risk alleles in TREM2 illuminate innate immunity in Alzheimer's disease
Golde, T. E., Streit, W. J., & Chakrabarty, P. (2013) · Alzheimer s Research & Therapy · doi:10.1186/alzrt178 · Cited by 39
Engelman, C. D., Koscik, R. L., Jonaitis, E. M., Hermann, B. P., Rue, A. L., & Sager, M. A. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.11.013 · Cited by 9
Research works printed but not linked: 1
- Rajagopalan P, 2013, TREM2 and neurodegenerative disease, The N Engl J Med, 369, 1565
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Metadata
- Authors
- Roussos, P., Katsel, P., Fam, P., Tan, W., Purohit, D. P., & Haroutunian, V.
- Affiliations
- New York/New Jersey VA Health Care Network (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Haroutunian, Vahram
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2014-12-09
- Volume
- 11
- Issue
- 10
- Pages
- 1163-1170
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC4461564
- OpenAlex
- W2102675610
- Cited by
- 103
- References
- 52
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 11 · 2023: 8 · 2022: 18 · 2021: 8 · 2020: 6 · 2019: 9 · 2018: 9 · 2017: 9 · 2016: 7 · 2015: 3
- FWCI
- 3.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (P01‐AG02219, P50‐AG05138, MH066392)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- TREM2, Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Brain, Female, Humans, Inflammation, Membrane Glycoproteins, Receptors, Immunologic, Risk, Interleukin-4, Gene Expression, Case-Control Studies, Mutation, Missense, Myeloid Cells, Apolipoprotein E4, Genetic Association Studies, Plaque, Amyloid
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