TREM2

Summary

Gene Symbol: TREM2
Description: triggering receptor expressed on myeloid cells 2
Alias: TREM-2, Trem2a, Trem2b, Trem2c, triggering receptor expressed on myeloid cells 2, triggering receptor expressed on monocytes 2, triggering receptor expressed on myeloid cells 2a
Species: human
Products:     TREM2

Top Publications

  1. Bouchon A, Dietrich J, Colonna M. Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes. J Immunol. 2000;164:4991-5 pubmed
    ..To mediate activation, TREM-1 associates with the transmembrane adapter molecule DAP12. Thus, TREM-1 mediates activation of neutrophil and monocytes, and may have a predominant role in inflammatory responses. ..
  2. Paloneva J, Mandelin J, Kiialainen A, Bohling T, Prudlo J, Hakola P, et al. DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features. J Exp Med. 2003;198:669-75 pubmed
    ..earlier characterized the molecular genetic background of PLOSL by identifying mutations in two genes, DAP12 and TREM2. DAP12 is a transmembrane adaptor protein that associates with the cell surface receptor TREM2...
  3. Chouery E, Delague V, Bergougnoux A, Koussa S, Serre J, Megarbane A. Mutations in TREM2 lead to pure early-onset dementia without bone cysts. Hum Mutat. 2008;29:E194-204 pubmed publisher
    ..40+3delAGG, in the 5' consensus donor splice site in intron 1 of TREM2 gene which is known to be responsible for PLOSL (Polycystic Lipomembranous Osteodysplasia with Sclerosing ..
  4. Rayaprolu S, Mullen B, Baker M, Lynch T, Finger E, Seeley W, et al. TREM2 in neurodegeneration: evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson's disease. Mol Neurodegener. 2013;8:19 pubmed publisher
    A rare variant in the Triggering Receptor Expressed on Myeloid cells 2 (TREM2) gene has been reported to be a genetic risk factor for Alzheimer's disease by two independent groups (Odds ratio between 2.9-4.5)...
  5. Wunderlich P, Glebov K, Kemmerling N, Tien N, Neumann H, Walter J. Sequential proteolytic processing of the triggering receptor expressed on myeloid cells-2 (TREM2) protein by ectodomain shedding and ?-secretase-dependent intramembranous cleavage. J Biol Chem. 2013;288:33027-36 pubmed publisher
    Triggering receptor expressed on myeloid cells-2 (TREM2) and its signaling adaptor protein TYROBP/DAP12 play important roles in signal transduction in dendritic cells, osteoclasts, tissue macrophages, and microglia...
  6. Cady J, Koval E, Benítez B, Zaidman C, Jockel Balsarotti J, Allred P, et al. TREM2 variant p.R47H as a risk factor for sporadic amyotrophic lateral sclerosis. JAMA Neurol. 2014;71:449-53 pubmed publisher
    ..Recently, a rare missense variant (p.R47H) in the microglial activating gene TREM2 was found to increase the risk of several neurodegenerative diseases, including Alzheimer disease. Whether the p...
  7. Paloneva J, Manninen T, Christman G, Hovanes K, Mandelin J, Adolfsson R, et al. Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype. Am J Hum Genet. 2002;71:656-62 pubmed
    ..Here we complete the molecular pathology of PLOSL by identifying TREM2 as the second PLOSL gene...
  8. Giraldo M, Lopera F, Siniard A, Corneveaux J, Schrauwen I, Carvajal J, et al. Variants in triggering receptor expressed on myeloid cells 2 are associated with both behavioral variant frontotemporal lobar degeneration and Alzheimer's disease. Neurobiol Aging. 2013;34:2077.e11-8 pubmed publisher
    Recent evidence suggests that rare genetic variants within the TREM2 gene are associated with increased risk of Alzheimer's disease...
  9. Forabosco P, Ramasamy A, Trabzuni D, Walker R, Smith C, Bras J, et al. Insights into TREM2 biology by network analysis of human brain gene expression data. Neurobiol Aging. 2013;34:2699-714 pubmed publisher
    Rare variants in TREM2 cause susceptibility to late-onset Alzheimer's disease...

More Information

Publications117 found, 100 shown here

  1. Bouchon A, Hernandez Munain C, Cella M, Colonna M. A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells. J Exp Med. 2001;194:1111-22 pubmed
    ..In contrast to Toll-like receptor-mediated signaling, TREM2/DAP12 stimulation is independent of nuclear factor-kappaB and p38 stress-activated protein kinase...
  2. Montalbetti L, Ratti M, Greco B, Aprile C, Moglia A, Soragna D. Neuropsychological tests and functional nuclear neuroimaging provide evidence of subclinical impairment in Nasu-Hakola disease heterozygotes. Funct Neurol. 2005;20:71-5 pubmed
    ..99mTc-ECD SPECT) and neuropsychological study of healthy members of an Italian family carrying a mutation in the TREM2 gene...
  3. Kiialainen A, Veckman V, Saharinen J, Paloneva J, Gentile M, Hakola P, et al. Transcript profiles of dendritic cells of PLOSL patients link demyelinating CNS disorders with abnormalities in pathways of actin bundling and immune response. J Mol Med (Berl). 2007;85:971-83 pubmed
    ..leukoencephalopathy (PLOSL), an early onset dementia with bone fractures caused by mutations in TYROBP (DAP12) and TREM2 genes, which encode important signaling molecules in human dendritic cells (DCs)...
  4. Frank S, Burbach G, Bonin M, Walter M, Streit W, Bechmann I, et al. TREM2 is upregulated in amyloid plaque-associated microglia in aged APP23 transgenic mice. Glia. 2008;56:1438-47 pubmed publisher
    ..One of these genes is the microglia-associated triggering receptor expressed on myeloid cells (TREM2) which enhances phagocytosis, but abrogates cytokine production as well as TLR and Fc receptor-mediated induction ..
  5. Stefano L, Racchetti G, Bianco F, Passini N, Gupta R, Panina Bordignon P, et al. The surface-exposed chaperone, Hsp60, is an agonist of the microglial TREM2 receptor. J Neurochem. 2009;110:284-94 pubmed publisher
    ..So far, specific agonist(s) of TREM2 have not been identified and its (their) transduction mechanisms are largely unknown...
  6. Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson P, Snaedal J, et al. Variant of TREM2 associated with the risk of Alzheimer's disease. N Engl J Med. 2013;368:107-16 pubmed publisher
    ..A rare missense mutation (rs75932628-T) in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2), which was predicted to result in an R47H substitution, was found to confer a ..
  7. Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, et al. TREM2 variants in Alzheimer's disease. N Engl J Med. 2013;368:117-27 pubmed publisher
    Homozygous loss-of-function mutations in TREM2, encoding the triggering receptor expressed on myeloid cells 2 protein, have previously been associated with an autosomal recessive form of early-onset dementia...
  8. Porrini V, Lanzillotta A, Branca C, Benarese M, Parrella E, Lorenzini L, et al. CHF5074 (CSP-1103) induces microglia alternative activation in plaque-free Tg2576 mice and primary glial cultures exposed to beta-amyloid. Neuroscience. 2015;302:112-20 pubmed publisher
    ..iNOS), and anti-inflammatory/phagocytic (M2) markers Mannose Receptor type C 1 (MRC1/CD206), Triggering Receptor Expressed on Myeloid cells 2 (TREM2) and Chitinase 3-like 3 (Ym1)...
  9. Morris G, Berk M, Maes M, Puri B. Could Alzheimer's Disease Originate in the Periphery and If So How So?. Mol Neurobiol. 2019;56:406-434 pubmed publisher
    ..In particular, as a result of increased activity of triggering receptor expressed on myeloid cells 2 (TREM-2), the presence of the apolipoprotein E4 (ApoE4) isoform, and changes in ANK1 ..
  10. Aredo B, Li T, Chen X, Zhang K, Wang C, Gou D, et al. A chimeric Cfh transgene leads to increased retinal oxidative stress, inflammation, and accumulation of activated subretinal microglia in mice. Invest Ophthalmol Vis Sci. 2015;56:3427-40 pubmed publisher
    ..Our data suggest that altered interactions of Cfh with MDA-modified proteins may be relevant in explaining the effects of the Cfh variant. ..
  11. Seitz S, Clarke P, Tyler K. Pharmacologic Depletion of Microglia Increases Viral Load in the Brain and Enhances Mortality in Murine Models of Flavivirus-Induced Encephalitis. J Virol. 2018;92: pubmed publisher
    ..In contrast, and as expected, expression of the macrophage marker triggering receptor expressed on myeloid cells 2 (TREM2) was decreased in virus-infected, PLX5622-treated mice compared to virus-infected ..
  12. Amos P, Fung S, Case A, Kifelew J, Osnis L, Smith C, et al. Modulation of Hematopoietic Lineage Specification Impacts TREM2 Expression in Microglia-Like Cells Derived From Human Stem Cells. ASN Neuro. 2017;9:1759091417716610 pubmed publisher
    ..cells with microglia morphology expressing a repertoire of markers associated with microglia: Iba1, CX3CR1, CD11b, TREM2, HexB, and P2RY12...
  13. Mecca C, Giambanco I, Donato R, Arcuri C. Microglia and Aging: The Role of the TREM2-DAP12 and CX3CL1-CX3CR1 Axes. Int J Mol Sci. 2018;19: pubmed publisher
    ..In the central nervous system (CNS), Triggering Receptor Expressed on Myeloid Cells 2-DNAX activation protein 12 (TREM2-DAP12) is a signaling complex expressed exclusively in ..
  14. Mathews S, Branch Woods A, Katano I, Makarov E, Thomas M, Gendelman H, et al. Human Interleukin-34 facilitates microglia-like cell differentiation and persistent HIV-1 infection in humanized mice. Mol Neurodegener. 2019;14:12 pubmed publisher
    ..expressed canonical human microglial cell markers that included CD14, CD68, CD163, CD11b, ITGB2, CX3CR1, CSFR1, TREM2 and P2RY12...
  15. Phongsisay V. The immunobiology of Campylobacter jejuni: Innate immunity and autoimmune diseases. Immunobiology. 2016;221:535-43 pubmed publisher
    ..immunoglobulin-like lectins (Siglecs), macrophage galactose-type lectin (MGL), and immunoglobulin-like receptors (TREM2, LMIR5/CD300b). The roles of these innate receptors and signaling molecules have been extensively studied...
  16. Beckmann N, Giorgetti E, Neuhaus A, Zurbruegg S, Accart N, Smith P, et al. Brain region-specific enhancement of remyelination and prevention of demyelination by the CSF1R kinase inhibitor BLZ945. Acta Neuropathol Commun. 2018;6:9 pubmed publisher
    ..dysfunction in the external capsule with an increase of myelin debris was obvious in triggering receptor expressed on myeloid cells 2 (TREM2) knock-out mice treated with cuprizone...
  17. Wang H, Li Y, Ryder J, Hole J, Ebert P, Airey D, et al. Genome-wide RNAseq study of the molecular mechanisms underlying microglia activation in response to pathological tau perturbation in the rTg4510 tau transgenic animal model. Mol Neurodegener. 2018;13:65 pubmed publisher
    ..The expression of many AD associated genes such as APOE and TREM2 was also altered in rTg4510 microglia cells...
  18. Guerreiro R, Lohmann E, Brás J, Gibbs J, Rohrer J, Gurunlian N, et al. Using exome sequencing to reveal mutations in TREM2 presenting as a frontotemporal dementia-like syndrome without bone involvement. JAMA Neurol. 2013;70:78-84 pubmed publisher
    ..Relatives were screened when appropriate. Mutations in the triggering receptor expressed on myeloid cells 2 gene (TREM2)...
  19. Cochain C, Vafadarnejad E, Arampatzi P, Pelisek J, Winkels H, Ley K, et al. Single-Cell RNA-Seq Reveals the Transcriptional Landscape and Heterogeneity of Aortic Macrophages in Murine Atherosclerosis. Circ Res. 2018;122:1661-1674 pubmed publisher
    ..aortas, comprising inflammatory macrophages showing enrichment in Il1b and previously undescribed TREM2hi (triggered receptor expressed on myeloid cells 2) macrophages showing enrichment in Trem2...
  20. Bisht K, Sharma K, Lecours C, Sánchez M, El Hajj H, Milior G, et al. Dark microglia: A new phenotype predominantly associated with pathological states. Glia. 2016;64:826-39 pubmed publisher
    ..mice), and strongly express CD11b and microglia-specific 4D4 in their processes encircling synaptic elements, and TREM2 when they associate with amyloid plaques...
  21. Teter B, Morihara T, Lim G, Chu T, Jones M, Zuo X, et al. Curcumin restores innate immune Alzheimer's disease risk gene expression to ameliorate Alzheimer pathogenesis. Neurobiol Dis. 2019;127:432-448 pubmed publisher
    Alzheimer's disease (AD) genetics implies a causal role for innate immune genes, TREM2 and CD33, products that oppose each other in the downstream Syk tyrosine kinase pathway, activating microglial phagocytosis of amyloid (Aβ)...
  22. Rudick C, Miyamoto T, Lang M, Agrawal D. Triggering receptor expressed on myeloid cells in the pathogenesis of periodontitis: potential novel treatment strategies. Expert Rev Clin Immunol. 2017;13:1189-1197 pubmed publisher
  23. Castillo E, Leon J, Mazzei G, Abolhassani N, Haruyama N, Saito T, et al. Comparative profiling of cortical gene expression in Alzheimer's disease patients and mouse models demonstrates a link between amyloidosis and neuroinflammation. Sci Rep. 2017;7:17762 pubmed publisher
    ..had altered expression of genes (Abi3, Apoe, Bin2, Cd33, Ctsc, Dock2, Fcer1g, Frmd6, Hck, Inpp5D, Ly86, Plcg2, Trem2, Tyrobp) defined as risk factors for AD by genome-wide association study or identified as genetic nodes in late-..
  24. Hu L, Zhou Y, Cui W, Hu X, DU L, Mi W, et al. Triggering receptor expressed on myeloid cells 2 (TREM2) dependent microglial activation promotes cisplatin-induced peripheral neuropathy in mice. Brain Behav Immun. 2018;68:132-145 pubmed publisher
    ..Furthermore, cisplatin enhanced triggering receptor expressed on myeloid cells 2 (TREM2) /DNAX-activating protein of 12 kDa (DAP12) signaling in the spinal cord microglia...
  25. Lefterov I, Schug J, Mounier A, Nam K, Fitz N, Koldamova R. RNA-sequencing reveals transcriptional up-regulation of Trem2 in response to bexarotene treatment. Neurobiol Dis. 2015;82:132-140 pubmed publisher
    ..ChIP) followed by ChIP-QPCR, and RT-QPCR expression assays were used to validate select genes, including Trem2, Tyrobp, Apoe and Ttr, differentially expressed in response to Retinoid X Receptor (RXR) activation...
  26. Möhle L, Israel N, Paarmann K, Krohn M, Pietkiewicz S, Müller A, et al. Chronic Toxoplasma gondii infection enhances ?-amyloid phagocytosis and clearance by recruited monocytes. Acta Neuropathol Commun. 2016;4:25 pubmed publisher
    ..The F4/80(+)?Ly6C(low) macrophages expressed high levels of Triggering Receptor Expressed on Myeloid cells 2 (TREM2), CD36, and Scavenger Receptor A1 (SCARA1), indicating phagocytic activity...
  27. Puntambekar S, Saber M, Lamb B, Kokiko Cochran O. Cellular players that shape evolving pathology and neurodegeneration following traumatic brain injury. Brain Behav Immun. 2018;71:9-17 pubmed publisher
    ..and macrophage receptors, namely CCR2, CX3CR1 and Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) in pathological neuroinflammation and neurodegeneration vs. recovery following TBI...
  28. Phongsisay V, Iizasa E, Hara H, Yoshida H. Evidence for TLR4 and FcRγ-CARD9 activation by cholera toxin B subunit and its direct bindings to TREM2 and LMIR5 receptors. Mol Immunol. 2015;66:463-71 pubmed publisher
    ..CTB targeted not only GM1 and TLR4 but also TREM2 and LMIR5/CD300b. CTB-TREM2 interaction initiated signal transduction through adaptor protein DAP12...
  29. Bhattacharjee S, Zhao Y, Dua P, Rogaev E, Lukiw W. microRNA-34a-Mediated Down-Regulation of the Microglial-Enriched Triggering Receptor and Phagocytosis-Sensor TREM2 in Age-Related Macular Degeneration. PLoS ONE. 2016;11:e0150211 pubmed publisher
    ..The triggering receptor expressed in myeloid/microglial cells-2 (TREM2), a trans-membrane-spanning, sensor-receptor of the immune-globulin/lectin-like gene superfamily is a critical ..
  30. Aryanpour R, Pasbakhsh P, Zibara K, Namjoo Z, Beigi Boroujeni F, Shahbeigi S, et al. Progesterone therapy induces an M1 to M2 switch in microglia phenotype and suppresses NLRP3 inflammasome in a cuprizone-induced demyelination mouse model. Int Immunopharmacol. 2017;51:131-139 pubmed publisher
    ..In summary, we reported for the first time that PRO therapy causes polarization of M2 microglia, attenuation of M1 phenotype, and suppression of NLRP3 inflammasome in a CPZ-induced demyelination model of MS. ..
  31. Engelman C, Darst B, Bilgel M, Vasiljevic E, Koscik R, Jedynak B, et al. The effect of rare variants in TREM2 and PLD3 on longitudinal cognitive function in the Wisconsin Registry for Alzheimer's Prevention. Neurobiol Aging. 2018;66:177.e1-177.e5 pubmed publisher
    Recent studies have found an association between functional variants in TREM2 and PLD3 and Alzheimer's disease (AD), but their effect on cognitive function is unknown...
  32. Takegahara N, Takamatsu H, Toyofuku T, Tsujimura T, Okuno T, Yukawa K, et al. Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis. Nat Cell Biol. 2006;8:615-22 pubmed
    ..These findings reveal an unexpected role for plexin-A1 and present a novel signalling mechanism for exerting the pleiotropic functions of semaphorins. ..
  33. Chen Y, Chen X, Guo X, Song W, Cao B, Wei Q, et al. Assessment of TREM2 rs75932628 association with Parkinson's disease and multiple system atrophy in a Chinese population. Neurol Sci. 2015;36:1903-6 pubmed publisher
    Although rs75932628 in triggering receptor expressed on myeloid cells 2 (TREM2) was shown to increase the risk for Alzheimer's disease, there is no agreement on the association between this variant and the risk for Parkinson's disease (PD)..
  34. Jay T, Hirsch A, Broihier M, Miller C, Neilson L, Ransohoff R, et al. Disease Progression-Dependent Effects of TREM2 Deficiency in a Mouse Model of Alzheimer's Disease. J Neurosci. 2017;37:637-647 pubmed publisher
    ..of immune-related genetic risk factors for AD, including coding variants in the gene TREM2 (triggering receptor expressed on myeloid cells 2)...
  35. Tan Y, Ng A, Vipin A, Lim J, Chander R, Ji F, et al. Higher Peripheral TREM2 mRNA Levels Relate to Cognitive Deficits and Hippocampal Atrophy in Alzheimer's Disease and Amnestic Mild Cognitive Impairment. J Alzheimers Dis. 2017;58:413-423 pubmed publisher
    Variants in triggering receptor expressed on myeloid cells 2 (TREM2) are associated with increased Alzheimer's disease (AD) risk...
  36. Darwent L, Carmona S, Lohmann E, Güven G, Kun Rodrigues C, Bilgic B, et al. Mutations in TYROBP are not a common cause of dementia in a Turkish cohort. Neurobiol Aging. 2017;58:240.e1-240.e3 pubmed publisher
    Mutations in TYROBP and TREM2 have been shown to cause polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy. Recently, variants in TREM2 were also associated with frontotemporal dementia and Alzheimer's disease...
  37. Sasaki A, Kakita A, Yoshida K, Konno T, Ikeuchi T, Hayashi S, et al. Variable expression of microglial DAP12 and TREM2 genes in Nasu-Hakola disease. Neurogenetics. 2015;16:265-76 pubmed publisher
    ..This extremely rare inherited disease is caused by mutations in either DAP12 or TREM2. The present study was designed to assess the relationship between DAP12/TREM2 genotype, mRNA and protein ..
  38. Lu Y, Liu W, Wang X. TREM2 variants and risk of Alzheimer's disease: a meta-analysis. Neurol Sci. 2015;36:1881-8 pubmed publisher
    Recent studies show that heterozygous variant of triggering receptor expressed on myeloid cells 2 (TREM2) increase the risk of Alzheimer's disease (AD) but with inconclusive results...
  39. Bertram L. Next Generation Sequencing in Alzheimer's Disease. Methods Mol Biol. 2016;1303:281-97 pubmed publisher
    ..Notable recent discoveries using NGS include the identification of rare susceptibility modifying alleles in APP, TREM2, and PLD3...
  40. Warnecke Eberz U, Metzger R, Hölscher A, Drebber U, Bollschweiler E. Diagnostic marker signature for esophageal cancer from transcriptome analysis. Tumour Biol. 2016;37:6349-58 pubmed publisher
    ..n = 19) have been clustered in a "diagnostic signature": PLA2G7, PRAME, MMP1, MMP3, MMP12, LIlRB2, TREM2, CHST2, IGFBP2, IGFBP7, KCNJ8, EMILIN2, CTHRC1, EMR2, WDR72, LPCAT1, COL4A2, CCL4, and SNX10...
  41. Henjum K, Almdahl I, Arskog V, Minthon L, Hansson O, Fladby T, et al. Cerebrospinal fluid soluble TREM2 in aging and Alzheimer's disease. Alzheimers Res Ther. 2016;8:17 pubmed publisher
    ..Mutant variants of triggering receptor expressed on myeloid cells 2 (TREM2) have recently been linked to late-onset AD and other neurodegenerative disorders...
  42. Zhong L, Zhang Z, Li X, Liao C, Mou P, Wang T, et al. TREM2/DAP12 Complex Regulates Inflammatory Responses in Microglia via the JNK Signaling Pathway. Front Aging Neurosci. 2017;9:204 pubmed publisher
    ..In particular, TREM1 acts as an amplifier of the immune response, while TREM2 functions as a negative regulator...
  43. Hickman S, El Khoury J. TREM2 and the neuroimmunology of Alzheimer's disease. Biochem Pharmacol. 2014;88:495-8 pubmed publisher
    ..two groups of investigators independently identified variants of the TREM2 gene, encoding triggering receptor expressed on myeloid cells 2 as causing increased susceptibility to late onset AD with an odds ratio similar to that of ..
  44. Satoh J, Kino Y, Motohashi N, Ishida T, Yagishita S, Jinnai K, et al. Immunohistochemical characterization of CD33 expression on microglia in Nasu-Hakola disease brains. Neuropathology. 2015;35:529-37 pubmed publisher
    ..caused by genetic mutations of either DNAX-activation protein 12 (DAP12) or triggering receptor expressed on myeloid cells 2 (TREM2)...
  45. Suárez Calvet M, Kleinberger G, Araque Caballero M, Brendel M, Rominger A, Alcolea D, et al. sTREM2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early-stage Alzheimer's disease and associate with neuronal injury markers. EMBO Mol Med. 2016;8:466-76 pubmed publisher
    b>TREM2 is an innate immune receptor expressed on the surface of microglia. Loss-of-function mutations of TREM2 are associated with increased risk of Alzheimer's disease (AD)...
  46. Kanatsu K, Tomita T. Molecular mechanisms of the genetic risk factors in pathogenesis of Alzheimer disease. Front Biosci (Landmark Ed). 2017;22:180-192 pubmed
    ..whole genome sequencing and exome sequencing have identified rare variants associated with LOAD, including TREM2...
  47. Wyatt S, Witt T, Barbaro N, Cohen Gadol A, Brewster A. Enhanced classical complement pathway activation and altered phagocytosis signaling molecules in human epilepsy. Exp Neurol. 2017;295:184-193 pubmed publisher
    ..was used to determine the levels of phagocytosis signaling proteins such as the complements C1q and C3, MerTK, Trem2, and Pros1 along with cleaved-caspase 3...
  48. Jiang T, Zhang Y, Gao Q, Ou Z, Gong P, Shi J, et al. TREM2 Ameliorates Neuronal Tau Pathology Through Suppression of Microglial Inflammatory Response. Inflammation. 2018;41:811-823 pubmed publisher
    As a recently identified susceptibility gene for Alzheimer's disease (AD), triggering receptor expressed on myeloid cells 2 (TREM2) encodes an immune receptor that is uniquely expressed on microglia, functioning as a modulator of ..
  49. Jin S, Benítez B, Karch C, Cooper B, Skorupa T, Carrell D, et al. Coding variants in TREM2 increase risk for Alzheimer's disease. Hum Mol Genet. 2014;23:5838-46 pubmed publisher
    The triggering receptor expressed on myeloid 2 (TREM2) is an immune phagocytic receptor expressed on brain microglia known to trigger phagocytosis and regulate the inflammatory response...
  50. Chen X, Chen Y, Wei Q, Guo X, Cao B, Ou R, et al. Assessment of TREM2 rs75932628 association with amyotrophic lateral sclerosis in a Chinese population. J Neurol Sci. 2015;355:193-5 pubmed publisher
    Although, rs75932628 in triggering receptor expressed on myeloid cells 2 (TREM2) was shown to increase the risk for Alzheimer's disease, there is no agreement on the association between this variant and the risk for amyotrophic lateral ..
  51. Yuan P, Condello C, Keene C, Wang Y, Bird T, Paul S, et al. TREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy. Neuron. 2016;90:724-39 pubmed publisher
    Haplodeficiency of the microglia gene TREM2 increases risk for late-onset Alzheimer's disease (AD) but the mechanisms remain uncertain...
  52. Saika R, Sakuma H, Noto D, Yamaguchi S, Yamamura T, Miyake S. MicroRNA-101a regulates microglial morphology and inflammation. J Neuroinflammation. 2017;14:109 pubmed publisher
    ..Finally, miR-101a downregulated the expression of MAPK phosphatase-1. miR-101a, which is enriched in the brain, promotes the differentiation of bone marrow cells into microglia-like cells. ..
  53. Zhong L, Wang Z, Wang D, Wang Z, Martens Y, Wu L, et al. Amyloid-beta modulates microglial responses by binding to the triggering receptor expressed on myeloid cells 2 (TREM2). Mol Neurodegener. 2018;13:15 pubmed publisher
    b>TREM2 is an innate immune receptor specifically expressed in microglia. Coding variations in TREM2 have been reported to increase the risk for Alzheimer's disease (AD) and other neurodegenerative diseases...
  54. Ma J, Zhou Y, Xu J, Liu X, Wang Y, Deng Y, et al. Association study of TREM2 polymorphism rs75932628 with late-onset Alzheimer's disease in Chinese Han population. Neurol Res. 2014;36:894-6 pubmed publisher
    We conducted a case-control study to investigate whether TREM2 polymorphism (rs75932628-T) was associated with late onset Alzheimer's disease in Chinese Southern Han population...
  55. Jiang T, Zhang Y, Chen Q, Gao Q, Zhu X, Zhou J, et al. TREM2 modifies microglial phenotype and provides neuroprotection in P301S tau transgenic mice. Neuropharmacology. 2016;105:196-206 pubmed publisher
    As a novel risk gene for Alzheimer's disease (AD), triggering receptor expressed on myeloid cells 2 (TREM2) gene encodes a type I transmembrane receptor that is uniquely expressed by the microglia in the brain...
  56. Scott Hewitt N, Folts C, Hogestyn J, Piester G, Mayer Proschel M, Noble M. Heterozygote galactocerebrosidase (GALC) mutants have reduced remyelination and impaired myelin debris clearance following demyelinating injury. Hum Mol Genet. 2017;26:2825-2837 pubmed publisher
    ..In addition, the microglial phagocytic response and elevation of Trem2, both necessary for clearing damaged myelin, were markedly reduced in GALC?+/- animals...
  57. Humphrey M, Nakamura M. A Comprehensive Review of Immunoreceptor Regulation of Osteoclasts. Clin Rev Allergy Immunol. 2016;51:48-58 pubmed publisher
    ..DAP12 pairs with a number of different immunoreceptors including triggering receptor expressed on myeloid cells 2 (TREM2), myeloid DAP12-associated lectin (MDL-1), and sialic acid-binding immunoglobulin-type ..
  58. Scott E, Penedo M, Murray J, Finno C. Defining Trends in Global Gene Expression in Arabian Horses with Cerebellar Abiotrophy. Cerebellum. 2017;16:462-472 pubmed publisher
    ..99, p < 0.01) and TREM2 (Log2(foldchange) = 2.02, p < 0.01)...
  59. Takahashi H, Klein Z, Bhagat S, Kaufman A, Kostylev M, Ikezu T, et al. Opposing effects of progranulin deficiency on amyloid and tau pathologies via microglial TYROBP network. Acta Neuropathol. 2017;133:785-807 pubmed publisher
    ..caused by PGRN deficiency-induced expression of TYROBP network genes (TNG) including an AD risk factor Trem2. PGRN-deficient APP/PS1 mice also exhibit less severe axonal dystrophy and partially improved behavior phenotypes...
  60. Pimenova A, Marcora E, Goate A. A Tale of Two Genes: Microglial Apoe and Trem2. Immunity. 2017;47:398-400 pubmed publisher
    ..2017) describe a gene expression signature associated with an APOE- and TREM2-dependent response of microglia to brain tissue damage that accumulates in aging and disease, defining an axis ..
  61. Varvel N, Grathwohl S, Degenhardt K, Resch C, Bosch A, Jucker M, et al. Replacement of brain-resident myeloid cells does not alter cerebral amyloid-β deposition in mouse models of Alzheimer's disease. J Exp Med. 2015;212:1803-9 pubmed publisher
    ..Interestingly, early after repopulation, infiltrating monocytes neither clustered around plaques nor showed Trem2 expression...
  62. Saber M, Kokiko Cochran O, Puntambekar S, Lathia J, Lamb B. Triggering Receptor Expressed on Myeloid Cells 2 Deficiency Alters Acute Macrophage Distribution and Improves Recovery after Traumatic Brain Injury. J Neurotrauma. 2017;34:423-435 pubmed publisher
    ..This includes genetic studies demonstrating that mutations in triggering receptor expressed on myeloid cells 2 (TREM2) is associated with a higher risk for not only AD but also multiple neurodegenerative ..
  63. Yin Z, Raj D, Saiepour N, Van Dam D, Brouwer N, Holtman I, et al. Immune hyperreactivity of A? plaque-associated microglia in Alzheimer's disease. Neurobiol Aging. 2017;55:115-122 pubmed publisher
    ..with similar Braak stages, expression of phagocytic markers and AD-associated genes, including HLA-DRA, APOE, AXL, TREM2, and TYROBP, was higher in laser-captured early-onset AD (EOAD) plaques than in late-onset AD plaques...
  64. Quan D, Cooper M, Potter J, Roberts M, Cheng H, Jarvis G. TREM-2 binds to lipooligosaccharides of Neisseria gonorrhoeae and is expressed on reproductive tract epithelial cells. Mucosal Immunol. 2008;1:229-38 pubmed publisher
    ..We conclude that gonococci can interact with TREM-2 receptors through binding to LOS and Opa protein and initiate cell signaling and cytokine production. ..
  65. Numasawa Y, Yamaura C, Ishihara S, Shintani S, Yamazaki M, Tabunoki H, et al. Nasu-Hakola disease with a splicing mutation of TREM2 in a Japanese family. Eur J Neurol. 2011;18:1179-83 pubmed publisher
    ..of progressive presenile dementia and formation of multifocal bone cysts, caused by genetic mutations of DAP12 and TREM2, which constitute a receptor/adapter signaling complex expressed on osteoclasts, dendritic cells, macrophages, and ..
  66. Gonzalez Murcia J, Schmutz C, Munger C, Perkes A, Gustin A, Peterson M, et al. Assessment of TREM2 rs75932628 association with Alzheimer's disease in a population-based sample: the Cache County Study. Neurobiol Aging. 2013;34:2889.e11-3 pubmed publisher
    Recent studies have identified the rs75932628 (R47H) variant in TREM2 as an Alzheimer's disease risk factor with estimated odds ratio ranging from 2.9 to 5.1...
  67. Kober D, Alexander Brett J, Karch C, Cruchaga C, Colonna M, Holtzman M, et al. Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms. elife. 2016;5: pubmed publisher
    Genetic variations in the myeloid immune receptor TREM2 are linked to several neurodegenerative diseases...
  68. Perez S, Nadeem M, He B, Miguel J, Malek Ahmadi M, Chen K, et al. Neocortical and hippocampal TREM2 protein levels during the progression of Alzheimer's disease. Neurobiol Aging. 2017;54:133-143 pubmed publisher
    Heterozygous triggering receptor expressed on myeloid cells (TREM2) mutations are an Alzheimer's disease (AD) risk factor. Nonmutated TREM2 dysregulation occurs in AD brain. Whether TREM2 is altered in prodromal AD remains unknown...
  69. Bellenguez C, Charbonnier C, Grenier Boley B, Quenez O, Le Guennec K, Nicolas G, et al. Contribution to Alzheimer's disease risk of rare variants in TREM2, SORL1, and ABCA7 in 1779 cases and 1273 controls. Neurobiol Aging. 2017;59:220.e1-220.e9 pubmed publisher
    ..damaging variants, we found exome-wide significant association between EOAD risk and rare variants in SORL1, TREM2, and ABCA7...
  70. Soragna D, Papi L, Ratti M, Sestini R, Tupler R, Montalbetti L. An Italian family affected by Nasu-Hakola disease with a novel genetic mutation in the TREM2 gene. J Neurol Neurosurg Psychiatry. 2003;74:825-6 pubmed
  71. Ortega Cubero S, Lorenzo Betancor O, Lorenzo E, Agúndez J, Jiménez Jiménez F, Ross O, et al. TREM2 R47H variant and risk of essential tremor: a cross-sectional international multicenter study. Parkinsonism Relat Disord. 2015;21:306-9 pubmed publisher
    ..Recently, a rare p.R47H substitution (rs75932628) in the TREM2 protein (triggering receptor expressed on myeloid cells 2; OMIM: *605086) has been proposed as a risk factor for AD, PD and amyotrophic lateral ..
  72. Colonna M, Wang Y. TREM2 variants: new keys to decipher Alzheimer disease pathogenesis. Nat Rev Neurosci. 2016;17:201-7 pubmed publisher
    Genome-wide association studies have identified rare variants of the gene that encodes triggering receptor expressed on myeloid cells 2 (TREM2) - an immune receptor that is found in brain microglia - as risk factors for non-familial ..
  73. Melchior B, Garcia A, Hsiung B, Lo K, Doose J, Thrash J, et al. Dual induction of TREM2 and tolerance-related transcript, Tmem176b, in amyloid transgenic mice: implications for vaccine-based therapies for Alzheimer's disease. ASN Neuro. 2010;2:e00037 pubmed publisher
    ..molecules previously implicated in decreasing the severity of autoimmune responses: TREM2 (triggering receptor expressed on myeloid cells 2) and the intracellular tolerance-associated transcript, Tmem176b (transmembrane domain ..
  74. Roussos P, Katsel P, Fam P, Tan W, Purohit D, Haroutunian V. The triggering receptor expressed on myeloid cells 2 (TREM2) is associated with enhanced inflammation, neuropathological lesions and increased risk for Alzheimer's dementia. Alzheimers Dement. 2015;11:1163-70 pubmed publisher
    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 ..
  75. Huang M, Wang D, Xu Z, Xu Y, Xu X, Ma Y, et al. Lack of genetic association between TREM2 and Alzheimer's disease in East Asian population: a systematic review and meta-analysis. Am J Alzheimers Dis Other Demen. 2015;30:541-6 pubmed publisher
    ..The goal of this systematic study and meta-analysis was to assess the association between Triggering receptor expressed on myeloid cells 2 (TREM2) variants and AD in East Asian population...
  76. Painter M, Atagi Y, Liu C, Rademakers R, Xu H, Fryer J, et al. TREM2 in CNS homeostasis and neurodegenerative disease. Mol Neurodegener. 2015;10:43 pubmed publisher
    ..The innate immune receptor and its adaptor protein—triggering receptor expressed on myeloid cells 2 (TREM2) and DNAX-activating protein of 12 kDa (DAP12)—possess the ability to modulate ..
  77. Bailey C, DeVaux L, Farzan M. The Triggering Receptor Expressed on Myeloid Cells 2 Binds Apolipoprotein E. J Biol Chem. 2015;290:26033-42 pubmed publisher
    The triggering receptor expressed on myeloid cells 2 (TREM2) is an Ig-like V-type receptor expressed by populations of myeloid cells in the central nervous system and periphery...
  78. Yeh F, Wang Y, Tom I, Gonzalez L, Sheng M. TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia. Neuron. 2016;91:328-40 pubmed publisher
    Genetic variants of TREM2, a protein expressed selectively by microglia in the brain, are associated with Alzheimer's disease (AD)...
  79. Benítez B, Cruchaga C. TREM2 and neurodegenerative disease. N Engl J Med. 2013;369:1567-8 pubmed publisher
  80. Lue L, Schmitz C, Serrano G, Sue L, Beach T, Walker D. TREM2 Protein Expression Changes Correlate with Alzheimer's Disease Neurodegenerative Pathologies in Post-Mortem Temporal Cortices. Brain Pathol. 2015;25:469-80 pubmed publisher
    Triggering receptor expressed by myeloid cells 2 (TREM2), a member of the immunoglobulin superfamily, has anti-inflammatory phagocytic function in myeloid cells...
  81. Ford J, McVicar D. TREM and TREM-like receptors in inflammation and disease. Curr Opin Immunol. 2009;21:38-46 pubmed publisher
    ..Together these new findings define the TREM and TREM-like receptors as pluripotent modifiers of disease through the integration of inflammatory signals with those associated with leukocyte adhesion. ..
  82. Mori Y, Yoshino Y, Ochi S, Yamazaki K, Kawabe K, Abe M, et al. TREM2 mRNA Expression in Leukocytes Is Increased in Alzheimer's Disease and Schizophrenia. PLoS ONE. 2015;10:e0136835 pubmed publisher
    b>TREM2 and TYROBP are causal genes for Nasu-Hakola disease (NHD), a rare autosomal recessive disease characterized by bone lesions and early-onset progressive dementia...
  83. Pottier C, Ravenscroft T, Brown P, Finch N, Baker M, Parsons M, et al. TYROBP genetic variants in early-onset Alzheimer's disease. Neurobiol Aging. 2016;48:222.e9-222.e15 pubmed publisher
    ..Overexpression of the p.D50_L51ins14 TYROBP mutant led to a profound reduction of TREM2 expression, a well-established risk factor for AD...
  84. Rohn T. The triggering receptor expressed on myeloid cells 2: "TREM-ming" the inflammatory component associated with Alzheimer's disease. Oxid Med Cell Longev. 2013;2013:860959 pubmed publisher
    ..Recently, a novel variant in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) has been identified that has refocused the spotlight back onto inflammation as a ..
  85. Cuyvers E, Bettens K, Philtjens S, Van Langenhove T, Gijselinck I, van der Zee J, et al. Investigating the role of rare heterozygous TREM2 variants in Alzheimer's disease and frontotemporal dementia. Neurobiol Aging. 2014;35:726.e11-9 pubmed publisher
    Homozygous mutations in exon 2 of TREM2, a gene involved in Nasu-Hakola disease, can cause frontotemporal dementia (FTD). Moreover, a rare TREM2 exon 2 variant (p...
  86. Jiao B, Liu X, Tang B, Hou L, Zhou L, Zhang F, et al. Investigation of TREM2, PLD3, and UNC5C variants in patients with Alzheimer's disease from mainland China. Neurobiol Aging. 2014;35:2422.e9-2422.e11 pubmed publisher
    ..R47H in TREM2, p.V232M in PLD3, and p.T835M in UNC5C...
  87. Jiang T, Tan L, Chen Q, Tan M, Zhou J, Zhu X, et al. A rare coding variant in TREM2 increases risk for Alzheimer's disease in Han Chinese. Neurobiol Aging. 2016;42:217.e1-3 pubmed publisher
    Two recent studies have identified that a rare coding variant (p.R47H) in exon 2 of triggering receptor expressed on myeloid cells 2 (TREM2) gene is associated with Alzheimer's disease (AD) susceptibility in Caucasians...
  88. Bonham L, Sirkis D, Fan J, Aparicio R, Tse M, Ramos E, et al. Identification of a rare coding variant in TREM2 in a Chinese individual with Alzheimer's disease. Neurocase. 2017;23:65-69 pubmed publisher
    Rare variation in the TREM2 gene is associated with a broad spectrum of neurodegenerative disorders including Alzheimer's disease (AD)...
  89. Sulonen A, Kallio S, Ellonen P, Suvela M, Elovaara I, Koivisto K, et al. No evidence for shared etiology in two demyelinative disorders, MS and PLOSL. J Neuroimmunol. 2009;206:86-90 pubmed publisher
    Loss-of-function mutations of DAP12 and TREM2 cause a recessively inherited disease PLOSL, manifesting in brain white matter. The genes of the DAP12-TREM2 signaling receptor are located on 19q13.12 and 6p21...
  90. Mengel D, Thelen M, Balzer Geldsetzer M, Söling C, Bach J, Schaeffer E, et al. TREM2 rare variant p.R47H is not associated with Parkinson's disease. Parkinsonism Relat Disord. 2016;23:109-11 pubmed publisher
    Variant p.R47H of triggering receptor expressed on myeloid cells 2 (TREM2) has been associated with Parkinson's disease (PD)...
  91. Belloli S, Pannese M, Buonsanti C, Maiorino C, Di Grigoli G, Carpinelli A, et al. Early upregulation of 18-kDa translocator protein in response to acute neurodegenerative damage in TREM2-deficient mice. Neurobiol Aging. 2017;53:159-168 pubmed publisher
    Mutations in the TREM2 gene confer risk for Alzheimer's disease and susceptibility for Parkinson's disease (PD)...
  92. Mazaheri F, Snaidero N, Kleinberger G, Madore C, Daria A, Werner G, et al. TREM2 deficiency impairs chemotaxis and microglial responses to neuronal injury. EMBO Rep. 2017;18:1186-1198 pubmed publisher
    Sequence variations in the triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to an increased risk for neurodegenerative disorders such as Alzheimer's disease and frontotemporal lobar degeneration...