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

Alzheimer's and Dementia

Volumn 11, Issue 10, 2015, Pages 1163-1170

  Roussos, Panos ^a,b   Katsel, Pavel ^a   Fam, Peter ^a   Tan, Weilun ^a   Purohit, Dushyant P ^a   Haroutunian, Vahram ^a,b  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Gene expression; Inflammation; Microglia; Mutation; Protein; TYROBP

Indexed keywords

ALPHA 2 MACROGLOBULIN; APOLIPOPROTEIN A1; BINDING PROTEIN; BIOLOGICAL MARKER; CYTOKINE; GAMMA INTERFERON; INTERLEUKIN 4; RANTES; TRIGGERING RECEPTOR EXPRESSED ON MYELOID CELLS 2; TYRO PROTEIN TYROSINE KINASE BINDING PROTEIN; UNCLASSIFIED DRUG; APOLIPOPROTEIN E4; IL4 PROTEIN, HUMAN; IMMUNOGLOBULIN RECEPTOR; MEMBRANE PROTEIN; TREM2 PROTEIN, HUMAN;

ALZHEIMER DISEASE; AMYLOID PLAQUE; ARTICLE; BRAIN REGION; CONTROLLED STUDY; DISEASE SEVERITY; DOWN REGULATION; GENE; GENE EXPRESSION; GENE FREQUENCY; GENETIC ASSOCIATION; GENETIC VARIABILITY; HUMAN; HUMAN TISSUE; MISSENSE MUTATION; NERVOUS SYSTEM INFLAMMATION; NEUROFIBRILLARY TANGLE; NEUROPATHOLOGY; PRIORITY JOURNAL; PROTEIN EXPRESSION; RISK FACTOR; T LYMPHOCYTE; TREM2 GENE; TYROBP GENE; UPREGULATION; BONE MARROW CELL; BRAIN; CASE CONTROL STUDY; FEMALE; GENETIC ASSOCIATION STUDY; GENETICS; INFLAMMATION; METABOLISM; PATHOLOGY; RISK;

ALZHEIMER DISEASE; APOLIPOPROTEIN E4; BRAIN; CASE-CONTROL STUDIES; FEMALE; GENE EXPRESSION; GENETIC ASSOCIATION STUDIES; HUMANS; INFLAMMATION; INTERLEUKIN-4; MEMBRANE GLYCOPROTEINS; MUTATION, MISSENSE; MYELOID CELLS; PLAQUE, AMYLOID; RECEPTORS, IMMUNOLOGIC; RISK;

EID: 84945443472     PISSN: 15525260     EISSN: 15525279     Source Type: Journal    
DOI: 10.1016/j.jalz.2014.10.013     Document Type: Article

References (50)

1. R. Guerreiro, A. Wojtas, J. Bras, M. Carrasquillo, E. Rogaeva, E. Majounie, and et al. TREM2 variants in Alzheimer's disease N Engl J Med 368 2013 117 127
2. T. Jonsson, H. Stefansson, S. Steinberg, I. Jonsdottir, P.V. Jonsson, J. Snaedal, and et al. Variant of TREM2 associated with the risk of Alzheimer's disease N Engl J Med 368 2013 107 116
3. B.A. Benitez, B. Cooper, P. Pastor, S.C. Jin, E. Lorenzo, S. Cervantes, and et al. TREM2 is associated with the risk of Alzheimer's disease in Spanish population Neurobiol Aging 34 2013 1711.e15 1711.e17
4. A. Ruiz, O. Dols-Icardo, M.J. Bullido, P. Pastor, E. Rodriguez-Rodriguez, A. Lopez de Munain, and et al. Assessing the role of the TREM2 p.R47H variant as a risk factor for Alzheimer's disease and frontotemporal dementia Neurobiol Aging 35 2014 444.e1 444.e4
5. C.D. Engelman, R.L. Koscik, E.M. Jonaitis, B.P. Hermann, A. La Rue, and M.A. Sager Investigation of triggering receptor expressed on myeloid cells 2 variant in the Wisconsin Registry for Alzheimer's Prevention Neurobiol Aging 35 2014 1252 1254
6. M. Giraldo, F. Lopera, A.L. Siniard, J.J. Corneveaux, I. Schrauwen, J. Carvajal, and 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 34 2013 2077.e11 2077.e18
7. J.D. Gonzalez Murcia, C. Schmutz, C. Munger, A. Perkes, A. Gustin, M. Peterson, and et al. Assessment of TREM2 rs75932628 association with Alzheimer's disease in a population-based sample: the Cache County Study Neurobiol Aging 34 2013 2889.e11 2889.e13
8. B. Zhang, C. Gaiteri, L.G. Bodea, Z. Wang, J. McElwee, A.A. Podtelezhnikov, and et al. Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer's disease Cell 153 2013 707 720
9. P. Rajagopalan, D.P. Hibar, and P.M. Thompson TREM2 and neurodegenerative disease The N Engl J Med 369 2013 1565 1567
10. S. Frank, G.J. Burbach, M. Bonin, M. Walter, W. Streit, I. Bechmann, and et al. TREM2 is upregulated in amyloid plaque-associated microglia in aged APP23 transgenic mice Glia 56 2008 1438 1447
11. K. Takahashi, C.D. Rochford, and H. Neumann Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2 J Exp Med 201 2005 647 657
12. T. Jiang, J.T. Yu, X.C. Zhu, and L. Tan TREM2 in Alzheimer's disease Mol Neurobiol 48 2013 180 185
13. T.E. Golde, W.J. Streit, and P. Chakrabarty Alzheimer's disease risk alleles in TREM2 illuminate innate immunity in Alzheimer's disease Alzheimers Res Ther 5 2013 24
14. C.L. Hsieh, M. Koike, S.C. Spusta, E.C. Niemi, M. Yenari, M.C. Nakamura, and et al. A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells by microglia J Neurochem 109 2009 1144 1156
15. V. Haroutunian, P. Katsel, and J. Schmeidler Transcriptional vulnerability of brain regions in Alzheimer's disease and dementia Neurobiol Aging 30 2009 561 573
16. K.L. Davis, R.C. Mohs, D. Marin, D.P. Purohit, D.P. Perl, M. Lantz, and et al. Cholinergic markers in elderly patients with early signs of Alzheimer disease JAMA 281 1999 1401 1406
17. V. Haroutunian, D.P. Perl, D.P. Purohit, D. Marin, K. Khan, M. Lantz, and et al. Regional distribution of neuritic plaques in the nondemented elderly and subjects with very mild Alzheimer disease Arch Neurol 55 1998 1185 1191
18. V. Haroutunian, D.P. Purohit, D.P. Perl, D. Marin, K. Khan, M. Lantz, and et al. Neurofibrillary tangles in nondemented elderly subjects and mild Alzheimer disease Arch Neurol 56 1999 713 718
19. S.S. Mirra, A. Heyman, D. McKeel, S.M. Sumi, B.J. Crain, L.M. Brownlee, and et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease Neurology 41 1991 479 486
20. J.C. Morris The Clinical Dementia Rating (CDR): current version and scoring rules Neurology 43 1993 2412 2414
21. G. Dooneief, K. Marder, M.X. Tang, and Y. Stern The Clinical Dementia Rating scale: community-based validation of "profound" and "terminal" stages Neurology 46 1996 1746 1749
22. H. Braak, and E. Braak Neuropathological staging of Alzheimer-related changes Acta Neuropathol 82 1991 239 259
23. P. Roussos, P. Katsel, K.L. Davis, P. Bitsios, S.G. Giakoumaki, J. Jogia, and et al. Molecular and genetic evidence for abnormalities in the nodes of Ranvier in schizophrenia Arch Gen Psychiatry 69 2012 7 15
24. P. Roussos, P. Katsel, K.L. Davis, S.G. Giakoumaki, L.J. Siever, P. Bitsios, and et al. Convergent findings for abnormalities of the NF-kappaB signaling pathway in schizophrenia Neuropsychopharmacology 38 2012 533 539
25. P. Roussos, P. Katsel, K.L. Davis, L.J. Siever, and V. Haroutunian A system-level transcriptomic analysis of schizophrenia using postmortem brain tissue samples Arch Gen Psychiatry 69 2012 1205 1213
26. J. Paloneva, T. Manninen, G. Christman, K. Hovanes, J. Mandelin, R. Adolfsson, and et al. Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype Am J Hum Genet 71 2002 656 662
27. G. Kleinberger, Y. Yamanishi, M. Suarez-Calvet, E. Czirr, E. Lohmann, E. Cuyvers, and et al. TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis Sci Transl Med 6 2014 243ra86
28. Y. Benjamini, and Y. Hochberg Controlling the false discovery rate: a practical and powerful approach to multiple testing J R Statist Soc B 57 1995 289 300
29. S. Purcell, B. Neale, K. Todd-Brown, L. Thomas, M.A. Ferreira, D. Bender, and et al. PLINK: a tool set for whole-genome association and population-based linkage analyses Am J Hum Genet 81 2007 559 575
30. T. Jonsson, J.K. Atwal, S. Steinberg, J. Snaedal, P.V. Jonsson, S. Bjornsson, and et al. A mutation in APP protects against Alzheimer's disease and age-related cognitive decline Nature 488 2012 96 99
31. Z. Abduljaleel, F.A. Al-Allaf, W. Khan, M. Athar, N. Shahzad, M.M. Taher, and et al. Evidence of trem2 variant associated with triple risk of Alzheimer's disease PLoS One 9 2014 e92648
32. P. Katsel, W. Tan, and V. Haroutunian Gain in brain immunity in the oldest-old differentiates cognitively normal from demented individuals PLoS One 4 2009 e7642
33. E.M. Blalock, J.W. Geddes, K.C. Chen, N.M. Porter, W.R. Markesbery, and P.W. Landfield Incipient Alzheimer's disease: microarray correlation analyses reveal major transcriptional and tumor suppressor responses Proc Natl Acad Sci U S A 101 2004 2173 2178
34. T. Wyss-Coray, and J. Rogers Inflammation in Alzheimer disease-a brief review of the basic science and clinical literature Cold Spring Harbor Perspect Med 2 2012 a006346
35. A. Parachikova, M.G. Agadjanyan, D.H. Cribbs, M. Blurton-Jones, V. Perreau, J. Rogers, and et al. Inflammatory changes parallel the early stages of Alzheimer disease Neurobiol Aging 28 2007 1821 1833
36. C. Vogel, and E.M. Marcotte Insights into the regulation of protein abundance from proteomic and transcriptomic analyses Nat Rev Genet 13 2012 227 232
37. H. Ito, and J.A. Hamerman TREM-2, triggering receptor expressed on myeloid cell-2, negatively regulates TLR responses in dendritic cells Eur J Immunol 42 2012 176 185
38. I.R. Turnbull, S. Gilfillan, M. Cella, T. Aoshi, M. Miller, L. Piccio, and et al. Cutting edge: TREM-2 attenuates macrophage activation J Immunol 177 2006 3520 3524
39. J.A. Hamerman, J.R. Jarjoura, M.B. Humphrey, M.C. Nakamura, W.E. Seaman, and L.L. Lanier Cutting edge: inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12 J Immunol 177 2006 2051 2055
40. J.A. Hamerman, N.K. Tchao, C.A. Lowell, and L.L. Lanier Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12 Nat Immunol 6 2005 579 586
41. G. Sessa, P. Podini, M. Mariani, A. Meroni, R. Spreafico, F. Sinigaglia, and et al. Distribution and signaling of TREM2/DAP12, the receptor system mutated in human polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy dementia Eur J Neurosci 20 2004 2617 2628
42. A. Aguzzi, B.A. Barres, and M.L. Bennett Microglia: scapegoat, saboteur, or something else? Science 339 2013 156 161
43. M.A. Meraz-Rios, D. Toral-Rios, D. Franco-Bocanegra, J. Villeda-Hernandez, and V. Campos-Pena Inflammatory process in Alzheimer's disease Front Integr Neurosci 7 2013 59
44. B. Melchior, A.E. Garcia, B.K. Hsiung, K.M. Lo, J.M. Doose, J.C. Thrash, and 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 2 2010 e00037
45. S. Rayaprolu, B. Mullen, M. Baker, T. Lynch, E. Finger, W.W. Seeley, and et al. TREM2 in neurodegeneration: evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson's disease Mol Neurodegener 8 2013 19
46. B. Borroni, F. Ferrari, D. Galimberti, B. Nacmias, C. Barone, S. Bagnoli, and et al. Heterozygous TREM2 mutations in frontotemporal dementia Neurobiol Aging 35 2014 934.e7 934.e10
47. E. Cuyvers, K. Bettens, S. Philtjens, T. Van Langenhove, I. Gijselinck, J. van der Zee, and et al. Investigating the role of rare heterozygous TREM2 variants in Alzheimer's disease and frontotemporal dementia Neurobiol Aging 35 2014 726.e11 726.e19
48. R. Medzhitov Origin and physiological roles of inflammation Nature 454 2008 428 435
49. M.W. Sieber, N. Jaenisch, M. Brehm, M. Guenther, B. Linnartz-Gerlach, H. Neumann, and et al. Attenuated inflammatory response in triggering receptor expressed on myeloid cells 2 (TREM2) knock-out mice following stroke PLoS One 8 2013 e52982
50. C. Cruchaga, J.S. Kauwe, O. Harari, S.C. Jin, Y. Cai, C.M. Karch, and et al. GWAS of cerebrospinal fluid tau levels identifies risk variants for Alzheimer's disease Neuron 78 2013 256 268