TREM2 Function in Alzheimer's Disease and Neurodegeneration

ACS Chemical Neuroscience

Volumn 7, Issue 4, 2016, Pages 420-427

  Ulrich, Jason D ^a   Holtzman, David M ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Alzheimer's disease; amyloid ; apolipoprotein E; microglia; neurodegeneration; TREM2

Indexed keywords

AMYLOID BETA PROTEIN; APOLIPOPROTEIN E; TAU PROTEIN; TRIGGERING RECEPTOR EXPRESSED ON MYELOID CELLS 2; IMMUNOGLOBULIN RECEPTOR; MEMBRANE PROTEIN; TREM2 PROTEIN, HUMAN;

ALZHEIMER DISEASE; CEREBROVASCULAR ACCIDENT; DISEASE MODEL; GENOME; GLIOSIS; HAPLOINSUFFICIENCY; HIPPOCAMPUS; MULTIPLE SCLEROSIS; NERVE DEGENERATION; PRION DISEASE; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; REVIEW; RISK FACTOR; AMYLOID PLAQUE; ANIMAL; CENTRAL NERVOUS SYSTEM; DEGENERATIVE DISEASE; GENETICS; HUMAN; METABOLISM; MICROGLIA; PATHOLOGY;

ALZHEIMER DISEASE; ANIMALS; CENTRAL NERVOUS SYSTEM; DISEASE MODELS, ANIMAL; HUMANS; MEMBRANE GLYCOPROTEINS; MICROGLIA; NEURODEGENERATIVE DISEASES; PLAQUE, AMYLOID; RECEPTORS, IMMUNOLOGIC;

EID: 84966393366     PISSN: None     EISSN: 19487193     Source Type: Journal    
DOI: 10.1021/acschemneuro.5b00313     Document Type: Review

References (64)

1. Jack, C. R., Jr. and Holtzman, D. M. (2013) Biomarker Modeling of Alzheimer's Disease Neuron 80, 1347-1358 10.1016/j.neuron.2013.12.003
2. Musiek, E. S. and Holtzman, D. M. (2015) Three dimensions of the amyloid hypothesis: time, space and 'wingmen Nat. Neurosci. 18, 800-806 10.1038/nn.4018
3. Kanekiyo, T., Xu, H., and Bu, G. (2014) ApoE and Aβ in Alzheimer's Disease: Accidental Encounters or Partners? Neuron 81, 740-754 10.1016/j.neuron.2014.01.045
4. Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., Hazrati, L., Collinge, J., Pocock, J., Lashley, T., Williams, J., Lambert, J.-C., Amouyel, P., Goate, A., Rademakers, R., Morgan, K., Powell, J., St. George-Hyslop, P., Singleton, A., and Hardy, J. (2013) TREM2 Variants in Alzheimer's Disease N. Engl. J. Med. 368, 117-127 10.1056/NEJMoa1211851
5. Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., Rujescu, D., Hampel, H., Giegling, I., Andreassen, O. A., Engedal, K., Ulstein, I., Djurovic, S., Ibrahim-Verbaas, C., Hofman, A., Ikram, M. A., van Duijn, C. M., Thorsteinsdottir, U., Kong, A., and Stefansson, K. (2013) Variant of TREM2 Associated with the Risk of Alzheimer's Disease N. Engl. J. Med. 368, 107-116 10.1056/NEJMoa1211103
6. Paloneva, J., Manninen, T., Christman, G., Hovanes, K., Mandelin, J., Adolfsson, R., Bianchin, M., Bird, T., Miranda, R., Salmaggi, A., Tranebjaerg, L., Konttinen, Y., and Peltonen, L. (2002) Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype Am. J. Hum. Genet. 71, 656-662 10.1086/342259
7. Paloneva, J., Autti, T., Raininko, R., Partanen, J., Salonen, O., Puranen, M., Hakola, P., and Haltia, M. (2001) CNS manifestations of Nasu-Hakola disease: A frontal dementia with bone cysts Neurology 56, 1552-1558 10.1212/WNL.56.11.1552
8. Jin, S., Carrasquillo, M., Benitez, B., Skorupa, T., Carrell, D., Patel, D., Lincoln, S., Krishnan, S., Kachadoorian, M., Reitz, C., Mayeux, R., Wingo, T., Lah, J., Levey, A., Murrell, J., Hendrie, H., Foroud, T., Graff-Radford, N., Goate, A., Cruchaga, C., and Ertekin-Taner, N. (2015) TREM2 is associated with increased risk for Alzheimer's disease in African Americans Mol. Neurodegener. 10, 19 10.1186/s13024-015-0016-9
9. Hooli, B. V., Parrado, A. R., Mullin, K., Yip, W.-K., Liu, T., Roehr, J. T., Qiao, D., Jessen, F., Peters, O., Becker, T., Ramirez, A., Lange, C., Bertram, L., and Tanzi, R. E. (2014) The rare TREM2 R47H variant exerts only a modest effect on Alzheimer disease risk Neurology 83, 1353-1358 10.1212/WNL.0000000000000855
10. Jin, S. C., Benitez, B. A., Karch, C. M., Cooper, B., Skorupa, T., Carrell, D., Norton, J. B., Hsu, S., Harari, O., Cai, Y., Bertelsen, S., Goate, A. M., and Cruchaga, C. (2014) Coding variants in TREM2 increase risk for Alzheimer's disease Hum. Mol. Genet. 23, 5838-5846 10.1093/hmg/ddu277
11. Replogle, J. M., Chan, G., White, C. C., Raj, T., Winn, P. A., Evans, D. A., Sperling, R. A., Chibnik, L. B., Bradshaw, E. M., Schneider, J. A., Bennett, D. A., and De Jager, P. L. (2015) A TREM1 variant alters the accumulation of Alzheimer-related amyloid pathology Ann. Neurol. 77, 469-477 10.1002/ana.24337
12. Benitez, B. A., Jin, S. C., Guerreiro, R., Graham, R., Lord, J., Harold, D., Sims, R., Lambert, J.-C., Gibbs, J. R., Bras, J., Sassi, C., Harari, O., Bertelsen, S., Lupton, M. K., Powell, J., Bellenguez, C., Brown, K., Medway, C., Haddick, P. C. G., van der Brug, M. P., Bhangale, T., Ortmann, W., Behrens, T., Mayeux, R., Pericak-Vance, M. A., Farrer, L. A., Schellenberg, G. D., Haines, J. L., Turton, J., Braae, A., Barber, I., Fagan, A. M., Holtzman, D. M., Morris, J. C., Williams, J., Kauwe, J. S. K., Amouyel, P., Morgan, K., Singleton, A., Hardy, J., Goate, A. M., and Cruchaga, C. (2014) Missense variant in TREML2 protects against Alzheimer's disease Neurobiol. Aging 35, 1510.e1519-1510.e1526 10.1016/j.neurobiolaging.2013.12.010
13. Bouchon, A., Dietrich, J., and Colonna, M. (2000) Cutting Edge: Inflammatory Responses Can Be Triggered by TREM-1, a Novel Receptor Expressed on Neutrophils and Monocytes J. Immunol. 164, 4991-4995 10.4049/jimmunol.164.10.4991
14. Feng, J., Call, M. E., and Wucherpfennig, K. W. (2006) The Assembly of Diverse Immune Receptors Is Focused on a Polar Membrane-Embedded Interaction Site PLoS Biol. 4, e142 10.1371/journal.pbio.0040142
15. N'Diaye, E.-N., Branda, C. S., Branda, S. S., Nevarez, L., Colonna, M., Lowell, C., Hamerman, J. A., and Seaman, W. E. (2009) TREM-2 (triggering receptor expressed on myeloid cells 2) is a phagocytic receptor for bacteria J. Cell Biol. 184, 215-223 10.1083/jcb.200808080
16. Takahashi, K., Rochford, C. D. P., and Neumann, H. (2005) Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2 J. Exp. Med. 201, 647-657 10.1084/jem.20041611
17. Kleinberger, G., Yamanishi, Y., Suárez-Calvet, M., Czirr, E., Lohmann, E., Cuyvers, E., Struyfs, H., Pettkus, N., Wenninger-Weinzierl, A., Mazaheri, F., Tahirovic, S., Lleó, A., Alcolea, D., Fortea, J., Willem, M., Lammich, S., Molinuevo, J. L., Sánchez-Valle, R., Antonell, A., Ramirez, A., Heneka, M. T., Sleegers, K., van der Zee, J., Martin, J.-J., Engelborghs, S., Demirtas-Tatlidede, A., Zetterberg, H., Van Broeckhoven, C., Gurvit, H., Wyss-Coray, T., Hardy, J., Colonna, M., and Haass, C. (2014) TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis Sci. Transl. Med. 6, 243ra286 10.1126/scitranslmed.3009093
18. Wang, Y., Cella, M., Mallinson, K., Ulrich, J. D., Young, K. L., Robinette, M. L., Gilfillan, S., Krishnan, G. M., Sudhakar, S., Zinselmeyer, B. H., Holtzman, D. M., Cirrito, J. R., and Colonna, M. (2015) TREM2 Lipid Sensing Sustains the Microglial Response in an Alzheimer's Disease Model Cell 160, 1061-1071 10.1016/j.cell.2015.01.049
19. Otero, K., Shinohara, M., Zhao, H., Cella, M., Gilfillan, S., Colucci, A., Faccio, R., Ross, F. P., Teitelbaum, S. L., Takayanagi, H., and Colonna, M. (2012) TREM2 and β-Catenin Regulate Bone Homeostasis by Controlling the Rate of Osteoclastogenesis J. Immunol. 188, 2612-2621 10.4049/jimmunol.1102836
20. Wu, K., Byers, D. E., Jin, X., Agapov, E., Alexander-Brett, J., Patel, A. C., Cella, M., Gilfilan, S., Colonna, M., Kober, D. L., Brett, T. J., and Holtzman, M. J. (2015) TREM-2 promotes macrophage survival and lung disease after respiratory viral infection J. Exp. Med. 212, 681-697 10.1084/jem.20141732
21. Hamerman, J. A., Jarjoura, J. R., Humphrey, M. B., Nakamura, M. C., Seaman, W. E., and Lanier, L. L. (2006) Cutting Edge: Inhibition of TLR and FcR Responses in Macrophages by Triggering Receptor Expressed on Myeloid Cells (TREM)-2 and DAP12 J. Immunol. 177, 2051-2055 10.4049/jimmunol.177.4.2051
22. Cannon, J., O'Driscoll, M., and Litman, G. (2012) Specific lipid recognition is a general feature of CD300 and TREM molecules Immunogenetics 64, 39-47 10.1007/s00251-011-0562-4
23. Poliani, P. L., Wang, Y., Fontana, E., Robinette, M. L., Yamanishi, Y., Gilfillan, S., and Colonna, M. (2015) TREM2 sustains microglial expansion during aging and response to demyelination J. Clin. Invest. 125, 2161-2170 10.1172/JCI77983
24. Atagi, Y., Liu, C.-C., Painter, M. M., Chen, X.-F., Verbeeck, C., Zheng, H., Li, X., Rademakers, R., Kang, S. S., Xu, H., Younkin, S., Das, P., Fryer, J. D., and Bu, G. (2015) Apolipoprotein E Is a Ligand for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) J. Biol. Chem. 290, 26043-26050 10.1074/jbc.M115.679043
25. Bailey, C. C., DeVaux, L. B., and Farzan, M. (2015) The Triggering Receptor Expressed on Myeloid Cells 2 Binds Apolipoprotein E J. Biol. Chem. 290, 26033-26042 10.1074/jbc.M115.677286
26. Jay, T. R., Miller, C. M., Cheng, P. J., Graham, L. C., Bemiller, S., Broihier, M. L., Xu, G., Margevicius, D., Karlo, J. C., Sousa, G. L., Cotleur, A. C., Butovsky, O., Bekris, L., Staugaitis, S. M., Leverenz, J. B., Pimplikar, S. W., Landreth, G. E., Howell, G. R., Ransohoff, R. M., and Lamb, B. T. (2015) TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer's disease mouse models J. Exp. Med. 212, 287-295 10.1084/jem.20142322
27. Frank, S., Burbach, G. J., Bonin, M., Walter, M., Streit, W., Bechmann, I., and Deller, T. (2008) TREM2 is upregulated in amyloid plaque-associated microglia in aged APP23 transgenic mice Glia 56, 1438-1447 10.1002/glia.20710
28. Chan, G., White, C. C., Winn, P. A., Cimpean, M., Replogle, J. M., Glick, L. R., Cuerdon, N. E., Ryan, K. J., Johnson, K. A., Schneider, J. A., Bennett, D. A., Chibnik, L. B., Sperling, R. A., Bradshaw, E. M., and De Jager, P. L. (2015) CD33 modulates TREM2: convergence of Alzheimer loci Nat. Neurosci. 18, 1556-1558 10.1038/nn.4126
29. Varvel, N. H., Grathwohl, S. A., Degenhardt, K., Resch, C., Bosch, A., Jucker, M., and Neher, J. J. (2015) Replacement of brain-resident myeloid cells does not alter cerebral amyloid-β deposition in mouse models of Alzheimer's disease J. Exp. Med. 212, 1803-1809 10.1084/jem.20150478
30. Matarin, M., Salih, D. A., Yasvoina, M., Cummings, D. M., Guelfi, S., Liu, W., Nahaboo Solim, M. A., Moens, T. G., Paublete, R. M., Ali, S. S., Perona, M., Desai, R., Smith, K. J., Latcham, J., Fulleylove, M., Richardson, J. C., Hardy, J., and Edwards, F. A. (2015) A Genome-wide Gene-Expression Analysis and Database in Transgenic Mice during Development of Amyloid or Tau Pathology Cell Rep. 10, 633-644 10.1016/j.celrep.2014.12.041
31. Ulrich, J. D., Finn, M. B., Wang, Y., Shen, A., Mahan, T. E., Jiang, H., Stewart, F. R., Piccio, L., Colonna, M., and Holtzman, D. M. (2014) Altered microglial response to Abeta plaques in APPPS1-21 mice heterozygous for TREM2 Mol. Neurodegener. 9, 20 10.1186/1750-1326-9-20
32. Korvatska, O., Leverenz, J. B., and Jayadev, S. et al. 2015, R47h variant of trem2 associated with alzheimer disease in a large late-onset family: Clinical, genetic, and neuropathological study JAMA Neurol. 72, 920-927 10.1001/jamaneurol.2015.0979
33. Prokop, S., Miller, K. R., Drost, N., Handrick, S., Mathur, V., Luo, J., Wegner, A., Wyss-Coray, T., and Heppner, F. L. (2015) Impact of peripheral myeloid cells on amyloid-β pathology in Alzheimer's disease-like mice J. Exp. Med. 212, 1811-1818 10.1084/jem.20150479
34. Sedgwick, J. D., Schwender, S., Imrich, H., Dörries, R., Butcher, G. W., and ter Meulen, V. (1991) Isolation and direct characterization of resident microglial cells from the normal and inflamed central nervous system Proc. Natl. Acad. Sci. U. S. A. 88, 7438-7442 10.1073/pnas.88.16.7438
35. Wang, Y., Szretter, K. J., Vermi, W., Gilfillan, S., Rossini, C., Cella, M., Barrow, A. D., Diamond, M. S., and Colonna, M. (2012) IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia Nat. Immunol. 13, 753-760 10.1038/ni.2360
36. Witmer-Pack, M. D., Hughes, D. A., Schuler, G., Lawson, L., McWilliam, A., Inaba, K., Steinman, R. M., and Gordon, S. (1993) Identification of macrophages and dendritic cells in the osteopetrotic (op/op) mouse J. Cell Sci. 104, 1021-1029
37. Dagher, N., Najafi, A., Kayala, K., Elmore, M., White, T., Medeiros, R., West, B., and Green, K. (2015) Colony-stimulating factor 1 receptor inhibition prevents microglial plaque association and improves cognition in 3xTg-AD mice J. Neuroinflammation 12, 139 10.1186/s12974-015-0366-9
38. 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., Fanek, Z., Liu, L., Chen, Z., Rothstein, J. D., Ransohoff, R. M., Gygi, S. P., Antel, J. P., and Weiner, H. L. (2014) Identification of a unique TGF-[beta]-dependent molecular and functional signature in microglia Nat. Neurosci. 17, 131-143 10.1038/nn.3599
39. Liu, Z., Condello, C., Schain, A., Harb, R., and Grutzendler, J. (2010) CX3CR1 in Microglia Regulates Brain Amyloid Deposition through Selective Protofibrillar Amyloid-β Phagocytosis J. Neurosci. 30, 17091-17101 10.1523/JNEUROSCI.4403-10.2010
40. Stalder, M., Deller, T., Staufenbiel, M., and Jucker, M. (2001) 3D-Reconstruction of microglia and amyloid in APP23 transgenic mice: no evidence of intracellular amyloid Neurobiol. Aging 22, 427-434 10.1016/S0197-4580(01)00209-3
41. Bolmont, T., Haiss, F., Eicke, D., Radde, R., Mathis, C. A., Klunk, W. E., Kohsaka, S., Jucker, M., and Calhoun, M. E. (2008) Dynamics of the Microglial/Amyloid Interaction Indicate a Role in Plaque Maintenance J. Neurosci. 28, 4283-4292 10.1523/JNEUROSCI.4814-07.2008
42. Guillot-Sestier, M.-V., Doty, K. R., Gate, D., Rodriguez, J., Leung, B. P., Rezai-Zadeh, K., and Town, T. (2015) Il10 Deficiency Rebalances Innate Immunity to Mitigate Alzheimer-Like Pathology Neuron 85, 534-548 10.1016/j.neuron.2014.12.068
43. Grathwohl, S. A., Kalin, R. E., Bolmont, T., Prokop, S., Winkelmann, G., Kaeser, S. A., Odenthal, J., Radde, R., Eldh, T., Gandy, S., Aguzzi, A., Staufenbiel, M., Mathews, P. M., Wolburg, H., Heppner, F. L., and Jucker, M. (2009) Formation and maintenance of Alzheimer's disease beta-amyloid plaques in the absence of microglia Nat. Neurosci. 12, 1361-1363 10.1038/nn.2432
44. Radde, R., Bolmont, T., Kaeser, S. A., Coomaraswamy, J., Lindau, D., Stoltze, L., Calhoun, M. E., Jäggi, F., Wolburg, H., Gengler, S., Haass, C., Ghetti, B., Czech, C., Hölscher, C., Mathews, P. M., and Jucker, M. (2006) Aβ42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology EMBO Rep. 7, 940-946 10.1038/sj.embor.7400784
45. Oakley, H., Cole, S. L., Logan, S., Maus, E., Shao, P., Craft, J., Guillozet-Bongaarts, A., Ohno, M., Disterhoft, J., Van Eldik, L., Berry, R., and Vassar, R. (2006) Intraneuronal β-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation J. Neurosci. 26, 10129-10140 10.1523/JNEUROSCI.1202-06.2006
46. Phimister, E. G. and Tanzi, R. E. (2015) TREM2 and Risk of Alzheimer's Disease-Friend or Foe? N. Engl. J. Med. 372, 2564-2565 10.1056/NEJMcibr1503954
47. Heppner, F. L., Ransohoff, R. M., and Becher, B. (2015) Immune attack: the role of inflammation in Alzheimer disease Nat. Rev. Neurosci. 16, 358-372 10.1038/nrn3880
48. Turnbull, I. R., Gilfillan, S., Cella, M., Aoshi, T., Miller, M., Piccio, L., Hernandez, M., and Colonna, M. (2006) Cutting Edge: TREM-2 Attenuates Macrophage Activation J. Immunol. 177, 3520-3524 10.4049/jimmunol.177.6.3520
49. Piccio, L., Buonsanti, C., Mariani, M., Cella, M., Gilfillan, S., Cross, A. H., Colonna, M., and Panina-Bordignon, P. (2007) Blockade of TREM-2 exacerbates experimental autoimmune encephalomyelitis Eur. J. Immunol. 37, 1290-1301 10.1002/eji.200636837
50. Cantoni, C., Bollman, B., Licastro, D., Xie, M., Mikesell, R., Schmidt, R., Yuede, C., Galimberti, D., Olivecrona, G., Klein, R., Cross, A., Otero, K., and Piccio, L. (2015) TREM2 regulates microglial cell activation in response to demyelination in vivo Acta Neuropathol. 129, 429-447 10.1007/s00401-015-1388-1
51. Hiremath, M. M., Saito, Y., Knapp, G. W., Ting, J. P. Y., Suzuki, K., and Matsushima, G. K. (1998) Microglial/macrophage accumulation during cuprizone-induced demyelination in C57BL/6 mice J. Neuroimmunol. 92, 38-49 10.1016/S0165-5728(98)00168-4
52. Takahashi, K., Prinz, M., Stagi, M., Chechneva, O., and Neumann, H. (2007) TREM2-Transduced Myeloid Precursors Mediate Nervous Tissue Debris Clearance and Facilitate Recovery in an Animal Model of Multiple Sclerosis PLoS Med. 4, e124 10.1371/journal.pmed.0040124
53. Piccio, L., Buonsanti, C., Cella, M., Tassi, I., Schmidt, R. E., Fenoglio, C., Rinker, J., Naismith, R. T., Panina-Bordignon, P., Passini, N., Galimberti, D., Scarpini, E., Colonna, M., and Cross, A. H. (2008) Identification of soluble TREM-2 in the cerebrospinal fluid and its association with multiple sclerosis and CNS inflammation Brain 131, 3081-3091 10.1093/brain/awn217
54. Zhu, C., Herrmann, U. S., Li, B., Abakumova, I., Moos, R., Schwarz, P., Rushing, E. J., Colonna, M., and Aguzzi, A. (2015) Triggering receptor expressed on myeloid cells-2 is involved in prion-induced microglial activation but does not contribute to prion pathogenesis in mouse brains Neurobiol. Aging 36, 1994-2003 10.1016/j.neurobiolaging.2015.02.019
55. Sieber, M. W., Jaenisch, N., Brehm, M., Guenther, M., Linnartz-Gerlach, B., Neumann, H., Witte, O. W., and Frahm, C. (2013) Attenuated inflammatory response in triggering receptor expressed on myeloid cells 2 (TREM2) knock-out mice following stroke PLoS One 8, e52982 10.1371/journal.pone.0052982
56. Kawabori, M., Kacimi, R., Kauppinen, T., Calosing, C., Kim, J. Y., Hsieh, C. L., Nakamura, M. C., and Yenari, M. A. (2015) Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) Deficiency Attenuates Phagocytic Activities of Microglia and Exacerbates Ischemic Damage in Experimental Stroke J. Neurosci. 35, 3384-3396 10.1523/JNEUROSCI.2620-14.2015
57. Condello, C., Yuan, P., Schain, A., and Grutzendler, J. (2015) Microglia constitute a barrier that prevents neurotoxic protofibrillar Aβ42 hotspots around plaques Nat. Commun. 6, 6176 10.1038/ncomms7176
58. Skerrett, R., Malm, T., and Landreth, G. (2014) Nuclear receptors in neurodegenerative diseases Neurobiol. Dis. 72, 104-116 10.1016/j.nbd.2014.05.019
59. Savage, J. C., Jay, T., Goduni, E., Quigley, C., Mariani, M. M., Malm, T., Ransohoff, R. M., Lamb, B. T., and Landreth, G. E. (2015) Nuclear Receptors License Phagocytosis by Trem2+ Myeloid Cells in Mouse Models of Alzheimer's Disease J. Neurosci. 35, 6532-6543 10.1523/JNEUROSCI.4586-14.2015
60. Maphis, N., Xu, G., Kokiko-Cochran, O. N., Jiang, S., Cardona, A., Ransohoff, R. M., Lamb, B. T., and Bhaskar, K. (2015) Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain Brain 138, 1738-1755 10.1093/brain/awv081
61. Asai, H., Ikezu, S., Tsunoda, S., Medalla, M., Luebke, J., Haydar, T., Wolozin, B., Butovsky, O., Kugler, S., and Ikezu, T. (2015) Depletion of microglia and inhibition of exosome synthesis halt tau propagation Nat. Neurosci. 18, 1584-1593 10.1038/nn.4132
62. Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., and Lee, V. M. Y. (2007) Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model Neuron 53, 337-351 10.1016/j.neuron.2007.01.010
63. Jaworski, T., Lechat, B., Demedts, D., Gielis, L., Devijver, H., Borghgraef, P., Duimel, H., Verheyen, F., Kügler, S., and Van Leuven, F. (2011) Dendritic Degeneration, Neurovascular Defects, and Inflammation Precede Neuronal Loss in a Mouse Model for Tau-Mediated Neurodegeneration Am. J. Pathol. 179, 2001-2015 10.1016/j.ajpath.2011.06.025
64. Bhaskar, K., Konerth, M., Kokiko-Cochran, O. N., Cardona, A., Ransohoff, R. M., and Lamb, B. T. (2010) Regulation of Tau Pathology by the Microglial Fractalkine Receptor Neuron 68, 19-31 10.1016/j.neuron.2010.08.023