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Immunity
04 16, 2019;50 (4): 955-974.

Immune Signaling in Neurodegeneration.

Timothy R Hammond, Samuel E Marsh, Beth Stevens
Author Information
  1. Timothy R Hammond: Boston Children's Hospital, F.M. Kirby Neurobiology Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  2. Samuel E Marsh: Boston Children's Hospital, F.M. Kirby Neurobiology Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  3. Beth Stevens: Boston Children's Hospital, F.M. Kirby Neurobiology Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA. Electronic address: beth.stevens@childrens.harvard.edu.
PMID: 30995509 DOI: 10.1016/j.immuni.2019.03.016

Abstract

Neurodegenerative diseases of the central nervous system progressively rob patients of their memory, motor function, and ability to perform daily tasks. Advances in genetics and animal models are beginning to unearth an unexpected role of the immune system in disease onset and pathogenesis; however, the role of cytokines, growth factors, and other immune signaling pathways in disease pathogenesis is still being examined. Here we review recent genetic risk and genome-wide association studies and emerging mechanisms for three key immune pathways implicated in disease, the growth factor TGF-β, the complement cascade, and the extracellular receptor TREM2. These immune signaling pathways are important under both healthy and neurodegenerative conditions, and recent work has highlighted new functional aspects of their signaling. Finally, we assess future directions for immune-related research in neurodegeneration and potential avenues for immune-related therapies.

Keywords

Alzheimer’s disease Complement Cytokine GWAS Inflammation Innate Immunity Microglia Neuro-immune Neurodegeneration Neuroinflammation Signaling TGF-β TREM2

References

  1. Neurology. 2017 Jul 4;89(1):88-100 [PMID: 28592453]
  2. Cell. 2016 May 5;165(4):921-35 [PMID: 27114033]
  3. Proc Natl Acad Sci U S A. 2016 Mar 1;113(9):E1316-25 [PMID: 26884167]
  4. Parkinsonism Relat Disord. 2019 Mar;60:25-31 [PMID: 30404763]
  5. Cold Spring Harb Perspect Biol. 2017 Apr 3;9(4): [PMID: 27940516]
  6. Neuron. 2016 Nov 23;92(4):796-812 [PMID: 27974162]
  7. Lancet. 2015 Oct 24;386(10004):1683-97 [PMID: 26595642]
  8. Mol Neurodegener. 2019 Jan 10;14(1):1 [PMID: 30630532]
  9. Ann Neurol. 1991 Oct;30(4):572-80 [PMID: 1789684]
  10. EMBO Mol Med. 2017 Oct;9(10):1356-1365 [PMID: 28855300]
  11. Brain Pathol. 2000 Jul;10(3):378-84 [PMID: 10885656]
  12. Neuroscience. 2015 Aug 27;302:89-102 [PMID: 25450953]
  13. Nat Genet. 2011 May;43(5):436-41 [PMID: 21460841]
  14. Neuron. 2011 Oct 20;72(2):257-68 [PMID: 21944779]
  15. Nat Genet. 2013 Dec;45(12):1452-8 [PMID: 24162737]
  16. Alzheimer Dis Assoc Disord. 2005 Apr-Jun;19(2):55-66 [PMID: 15942322]
  17. Neurology. 2003 May 13;60(9):1495-500 [PMID: 12743238]
  18. J Neuropathol Exp Neurol. 2012 May;71(5):362-81 [PMID: 22487856]
  19. Ann Neurol. 1997 Jan;41(1):17-24 [PMID: 9005861]
  20. JAMA Neurol. 2013 Feb;70(2):223-8 [PMID: 23407718]
  21. Nature. 1991 Feb 21;349(6311):704-6 [PMID: 1671712]
  22. Hum Mutat. 2008 Sep;29(9):E194-204 [PMID: 18546367]
  23. Nat Neurosci. 2018 Oct;21(10):1370-1379 [PMID: 30250265]
  24. Acta Neuropathol. 2018 Dec;136(6):821-853 [PMID: 30488277]
  25. J Biol Chem. 2015 Jun 19;290(25):15866-15877 [PMID: 25957402]
  26. Cell. 2017 Jun 15;169(7):1276-1290.e17 [PMID: 28602351]
  27. Lancet Neurol. 2014 Jul;13(7):686-99 [PMID: 24943344]
  28. Trends Neurosci. 2016 Nov;39(11):750-762 [PMID: 27776749]
  29. J Exp Med. 2005 Feb 21;201(4):647-57 [PMID: 15728241]
  30. Sci Transl Med. 2017 May 31;9(392): [PMID: 28566429]
  31. J Neurosci. 2014 Sep 3;34(36):11929-47 [PMID: 25186741]
  32. Proc Natl Acad Sci U S A. 2018 Oct 2;115(40):10172-10177 [PMID: 30232263]
  33. Ann Clin Transl Neurol. 2016 Nov 04;3(12):924-933 [PMID: 28097204]
  34. Int J Alzheimers Dis. 2010 Jun 22;2010: [PMID: 20721346]
  35. Brain. 2018 Jul 1;141(7):2194-2212 [PMID: 29733334]
  36. J Biol Chem. 2013 Nov 15;288(46):33027-36 [PMID: 24078628]
  37. Acta Neuropathol. 1991;82(4):239-59 [PMID: 1759558]
  38. Nat Rev Neurol. 2016 Jan;12(1):15-27 [PMID: 26635213]
  39. Brain. 2008 Nov;131(Pt 11):3081-91 [PMID: 18790823]
  40. Nat Neurosci. 2007 Nov;10(11):1387-94 [PMID: 17965659]
  41. Neuron. 2014 Dec 3;84(5):927-39 [PMID: 25467979]
  42. Neuron. 2018 Dec 19;100(6):1322-1336.e7 [PMID: 30392797]
  43. Nat Rev Neurol. 2018 Nov;14(11):667-675 [PMID: 30266932]
  44. Cell Tissue Res. 2004 Oct;318(1):121-34 [PMID: 15338272]
  45. Neurosci Lett. 2004 Sep 2;367(2):194-6 [PMID: 15331151]
  46. Nat Genet. 2010 Sep;42(9):781-5 [PMID: 20711177]
  47. Neuron. 2018 Mar 7;97(5):1023-1031.e7 [PMID: 29518356]
  48. Immunity. 2013 Jan 24;38(1):79-91 [PMID: 23273845]
  49. Neurology. 2001 Jun 12;56(11):1552-8 [PMID: 11402114]
  50. Front Cell Neurosci. 2014 Nov 21;8:393 [PMID: 25484855]
  51. Nat Genet. 2011 May;43(5):429-35 [PMID: 21460840]
  52. Brain Res. 2007 Oct 31;1178:132-40 [PMID: 17900537]
  53. Cell. 2018 Aug 9;174(4):1015-1030.e16 [PMID: 30096299]
  54. Mol Neurodegener. 2017 Jan 31;12(1):12 [PMID: 28143566]
  55. Nat Med. 2001 May;7(5):612-8 [PMID: 11329064]
  56. Sci Transl Med. 2014 Mar 19;6(228):228fs13 [PMID: 24648338]
  57. Cell. 2015 Mar 12;160(6):1061-71 [PMID: 25728668]
  58. Neurobiol Dis. 2019 Apr;124:276-288 [PMID: 30381260]
  59. Immunity. 2019 Jan 15;50(1):253-271.e6 [PMID: 30471926]
  60. J Neurosci. 2002 Sep 15;22(18):7873-8 [PMID: 12223540]
  61. Brain. 2017 May 1;140(5):1437-1446 [PMID: 28387812]
  62. Cold Spring Harb Perspect Med. 2011 Sep;1(1):a009316 [PMID: 22229125]
  63. Proc Natl Acad Sci U S A. 2013 Jun 4;110(23):9535-40 [PMID: 23690619]
  64. Transl Psychiatry. 2018 May 18;8(1):99 [PMID: 29777097]
  65. J Neurosci. 2014 Jun 4;34(23):7917-30 [PMID: 24899714]
  66. Nat Rev Immunol. 2007 Feb;7(2):155-61 [PMID: 17220916]
  67. Nat Cell Biol. 2009 Jul;11(7):909-13 [PMID: 19503072]
  68. Lancet Neurol. 2018 Aug;17(8):721-730 [PMID: 30033062]
  69. Nat Med. 2000 Aug;6(8):916-9 [PMID: 10932230]
  70. Neurology. 1990 Jan;40(1):1-8 [PMID: 2153271]
  71. Cell Rep. 2016 Aug 9;16(6):1690-1700 [PMID: 27475227]
  72. Microsc Res Tech. 2000 Aug 15;50(4):305-15 [PMID: 10936885]
  73. J Immunol. 2000 May 15;164(10):4991-5 [PMID: 10799849]
  74. Neurosci Lett. 1987 Aug 18;79(1-2):195-200 [PMID: 3670729]
  75. Neurology. 2005 May 10;64(9):1502-7 [PMID: 15883308]
  76. Dev Neurobiol. 2012 Jul;72(7):1068-84 [PMID: 22489086]
  77. Alzheimers Dement. 2018 Nov;14(11):1438-1449 [PMID: 29792870]
  78. J Cell Biol. 2009 Jan 26;184(2):215-23 [PMID: 19171755]
  79. J Biol Chem. 1998 Dec 4;273(49):32934-42 [PMID: 9830044]
  80. Neurology. 2018 Sep 18;91(12):e1182-e1195 [PMID: 30143564]
  81. Cold Spring Harb Perspect Med. 2012 Oct 01;2(10): [PMID: 22960626]
  82. Cold Spring Harb Perspect Med. 2012 Oct 01;2(10): [PMID: 23028126]
  83. J Alzheimers Dis. 2017;56(1):157-166 [PMID: 27911312]
  84. Nature. 2016 Aug 31;537(7618):50-6 [PMID: 27582220]
  85. Science. 2014 May 2;344(6183):519-23 [PMID: 24786080]
  86. Neuropsychopharmacology. 2014 Dec;39(13):2949-62 [PMID: 25047746]
  87. Immunogenetics. 2012 Jan;64(1):39-47 [PMID: 21800138]
  88. Neurology. 2012 Dec 11;79(24):2307-14 [PMID: 23152586]
  89. Science. 2016 May 6;352(6286):712-716 [PMID: 27033548]
  90. J Neurosci. 2008 Dec 24;28(52):14156-64 [PMID: 19109498]
  91. PLoS Med. 2018 Jan 9;15(1):e1002487 [PMID: 29315334]
  92. Am J Pathol. 1999 Mar;154(3):927-36 [PMID: 10079271]
  93. Annu Rev Neurosci. 2012;35:369-89 [PMID: 22715882]
  94. Neurobiol Aging. 2012 Jan;33(1):196.e29-40 [PMID: 20619937]
  95. Cold Spring Harb Perspect Med. 2012 Jan;2(1):a009381 [PMID: 22315722]
  96. Nat Immunol. 2006 Dec;7(12):1326-33 [PMID: 17086186]
  97. Nature. 1997 Aug 28;388(6645):839-40 [PMID: 9278044]
  98. J Neurol Neurosurg Psychiatry. 2014 Oct;85(10):1065-75 [PMID: 24691581]
  99. J Neurosci. 2017 Jul 12;37(28):6797-6809 [PMID: 28607171]
  100. PLoS One. 2010 Nov 15;5(11):e13950 [PMID: 21085570]
  101. J Neuroinflammation. 2009 Nov 17;6:35 [PMID: 19917141]
  102. Lancet Neurol. 2013 Feb;12(2):207-16 [PMID: 23332364]
  103. Immunity. 2017 Sep 19;47(3):566-581.e9 [PMID: 28930663]
  104. Annu Rev Genomics Hum Genet. 2002;3:67-99 [PMID: 12142353]
  105. Mov Disord. 2017 Feb;32(2):211-218 [PMID: 27886407]
  106. Annu Rev Cell Dev Biol. 2018 Oct 6;34:523-544 [PMID: 30089221]
  107. Science. 1993 Aug 13;261(5123):921-3 [PMID: 8346443]
  108. Lancet. 2015 Oct 24;386(10004):1672-82 [PMID: 26595641]
  109. Neuron. 2016 May 18;90(4):724-39 [PMID: 27196974]
  110. Nat Genet. 2017 Sep;49(9):1373-1384 [PMID: 28714976]
  111. Nat Neurosci. 2019 Dec;22(12):2111-2116 [PMID: 31659342]
  112. Nat Rev Neurosci. 2018 Oct;19(10):583-598 [PMID: 30194347]
  113. Methods. 2009 Jul;48(3):265-76 [PMID: 19303049]
  114. J Immunol. 2009 Jul 15;183(2):1375-83 [PMID: 19561098]
  115. Nat Rev Neurol. 2013 Feb;9(2):106-18 [PMID: 23296339]
  116. Neuron. 2017 Apr 19;94(2):278-293.e9 [PMID: 28426964]
  117. JAMA Neurol. 2014 Nov;71(11):1394-404 [PMID: 25199842]
  118. Nat Rev Neurosci. 2016 Jan;17(1):5-21 [PMID: 26631930]
  119. Acta Neuropathol. 2019 Jun;137(6):879-899 [PMID: 30739198]
  120. Neurosci Biobehav Rev. 2016 Sep;68:727-740 [PMID: 27422450]
  121. Neuron. 2018 Dec 19;100(6):1337-1353.e5 [PMID: 30415998]
  122. Cell. 2010 Jul 9;142(1):144-57 [PMID: 20603020]
  123. Neuron. 2011 Oct 20;72(2):245-56 [PMID: 21944778]
  124. Mol Psychiatry. 2020 Mar;25(3):629-639 [PMID: 29988083]
  125. J Neurosci. 2008 Jun 18;28(25):6333-41 [PMID: 18562603]
  126. EMBO Mol Med. 2016 Sep 01;8(9):992-1004 [PMID: 27402340]
  127. Alzheimers Dement. 2015 Jun;11(6):658-71 [PMID: 25533204]
  128. Lancet Neurol. 2018 Jan;17(1):64-74 [PMID: 29263008]
  129. Neurol Genet. 2016 Jul 26;2(4):e90 [PMID: 27504496]
  130. Lancet Neurol. 2015 Apr;14(4):388-405 [PMID: 25792098]
  131. J Parkinsons Dis. 2011;1(1):19-33 [PMID: 23275799]
  132. Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7975-80 [PMID: 20375278]
  133. J Clin Invest. 2009 Jan;119(1):182-92 [PMID: 19104149]
  134. Nat Neurosci. 2014 Jan;17(1):131-43 [PMID: 24316888]
  135. Neurobiol Aging. 2013 Aug;34(8):2077.e11-8 [PMID: 23582655]
  136. Alzheimers Res Ther. 2012 Apr 30;4(2):11 [PMID: 22546279]
  137. J Biol Chem. 1993 Nov 15;268(32):24374-84 [PMID: 8226987]
  138. J Exp Med. 2018 Apr 2;215(4):1047-1058 [PMID: 29483128]
  139. Science. 2010 Nov 5;330(6005):841-5 [PMID: 20966214]
  140. Front Cell Neurosci. 2014 Nov 07;8:380 [PMID: 25426028]
  141. J Exp Med. 2003 Aug 18;198(4):645-51 [PMID: 12913093]
  142. J Exp Med. 2015 Mar 9;212(3):287-95 [PMID: 25732305]
  143. EMBO J. 2017 Sep 1;36(17):2473-2487 [PMID: 28768718]
  144. Nat Genet. 2010 Mar;42(3):234-9 [PMID: 20154673]
  145. Am J Hum Genet. 2002 Sep;71(3):656-62 [PMID: 12080485]
  146. Nature. 2017 Jun 29;546(7660):656-661 [PMID: 28636593]
  147. Trends Immunol. 2001 Jun;22(6):337-42 [PMID: 11377294]
  148. J Neurosci. 2016 Jan 13;36(2):577-89 [PMID: 26758846]
  149. Nat Med. 2019 Mar;25(3):496-506 [PMID: 30692699]
  150. Nat Genet. 2013 Jun;45(6):580-5 [PMID: 23715323]
  151. Neuron. 2016 Jan 6;89(1):37-53 [PMID: 26687838]
  152. Immunol Rev. 2009 Nov;232(1):42-58 [PMID: 19909355]
  153. Elife. 2016 Dec 20;5: [PMID: 27995897]
  154. J Neuroimmune Pharmacol. 2008 Jun;3(2):130-40 [PMID: 18247125]
  155. PLoS One. 2015 Feb 06;10(2):e0116549 [PMID: 25658940]
  156. N Engl J Med. 2013 Jan 10;368(2):107-16 [PMID: 23150908]
  157. Nat Med. 2014 Jun;20(6):659-63 [PMID: 24793238]
  158. Nat Neurosci. 2019 Feb;22(2):191-204 [PMID: 30617257]
  159. Cell. 2007 Dec 14;131(6):1164-78 [PMID: 18083105]
  160. J Neurosci. 2006 Oct 4;26(40):10129-40 [PMID: 17021169]
  161. Neurobiol Dis. 2008 May;30(2):234-42 [PMID: 18356065]
  162. Nat Commun. 2015 Aug 18;6:7967 [PMID: 26284939]
  163. Neurology. 2015 Aug 25;85(8):692-700 [PMID: 26208959]
  164. Neuropathol Appl Neurobiol. 2019 Feb;45(1):81-87 [PMID: 30422329]
  165. Cell Rep. 2014 Sep 11;8(5):1271-9 [PMID: 25159150]
  166. Mol Cell Biol. 2003 Jun;23(12):4199-206 [PMID: 12773563]
  167. Curr Protoc Mouse Biol. 2014 Sep 03;4(3):121-39 [PMID: 25723963]
  168. Mol Neurodegener. 2013 Jun 21;8:19 [PMID: 23800361]
  169. Alzheimers Res Ther. 2018 Aug 16;10(1):79 [PMID: 30111356]
  170. Physiol Rev. 2001 Apr;81(2):741-66 [PMID: 11274343]
  171. Nature. 2015 Jul 16;523(7560):337-41 [PMID: 26030524]
  172. Ann Neurol. 1990 May;27(5):457-64 [PMID: 2360787]
  173. Neurology. 1988 Aug;38(8):1285-91 [PMID: 3399080]
  174. Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):11524-11529 [PMID: 29073081]
  175. J Neuroimmunol. 2011 Jul;236(1-2):39-46 [PMID: 21640391]
  176. Cold Spring Harb Perspect Biol. 2011 Mar 01;3(3): [PMID: 21068150]
  177. Acta Neuropathol. 1992;84(1):100-4 [PMID: 1502878]
  178. Cell Tissue Res. 2018 Jul;373(1):9-20 [PMID: 29536161]
  179. Mol Psychiatry. 2015 Nov;20(11):1294-300 [PMID: 26324103]
  180. Nat Rev Immunol. 2010 Jun;10(6):387-402 [PMID: 20467426]
  181. Mol Psychiatry. 2018 Feb;23(2):323-334 [PMID: 28093569]
  182. J Mol Neurosci. 2004;23(3):247-54 [PMID: 15181253]
  183. Nat Neurosci. 2014 May;17(5):661-3 [PMID: 24728269]
  184. Sci Transl Med. 2016 Dec 14;8(369):369ra178 [PMID: 27974666]
  185. N Engl J Med. 2013 Jan 10;368(2):117-27 [PMID: 23150934]
  186. Nature. 2015 Feb 19;518(7539):365-9 [PMID: 25693568]
  187. Nature. 2007 Nov 15;450(7168):435-9 [PMID: 17960135]
  188. Science. 1996 Oct 4;274(5284):99-102 [PMID: 8810256]
  189. EMBO Mol Med. 2017 Oct;9(10):1366-1378 [PMID: 28855301]
  190. Acta Neuropathol Commun. 2016 Jun 29;4(1):65 [PMID: 27357286]
  191. Nature. 2007 Nov 15;450(7168):430-4 [PMID: 17960134]
  192. Nature. 2017 Apr 27;544(7651):488-492 [PMID: 28424512]
  193. Nat Neurosci. 2017 Aug;20(8):1052-1061 [PMID: 28628103]
  194. J Immunol. 1994 May 15;152(10):5050-9 [PMID: 8176223]
  195. Mol Neurodegener. 2018 Mar 1;13(1):11 [PMID: 29490706]
  196. Neuron. 2018 Jun 27;98(6):1170-1183.e8 [PMID: 29861285]
  197. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11282-6 [PMID: 8248242]
  198. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10016-20 [PMID: 1438191]
  199. Nat Immunol. 2008 Oct;9(10):1091-4 [PMID: 18800157]
  200. Neuron. 2003 Dec 18;40(6):1133-45 [PMID: 14687548]
  201. Ann Neurol. 2008 Dec;64 Suppl 2:S81-92 [PMID: 19127578]
  202. Nat Med. 2017 Sep 8;23(9):1018-1027 [PMID: 28886007]
  203. Nat Genet. 2017 Oct;49(10):1511-1516 [PMID: 28892059]
  204. Nature. 2018 Aug;560(7717):185-191 [PMID: 30046111]
  205. Trends Mol Med. 2017 Jun;23(6):512-533 [PMID: 28442216]
  206. Nat Genet. 2014 Sep;46(9):989-93 [PMID: 25064009]
  207. Alzheimers Dement (N Y). 2018 Dec 17;4:746-755 [PMID: 30581980]
  208. Neurosci Lett. 1995 Jun 30;193(2):129-32 [PMID: 7478158]
  209. Nat Genet. 2019 Mar;51(3):414-430 [PMID: 30820047]
  210. Neuron. 2016 Jul 20;91(2):328-40 [PMID: 27477018]
  211. Neurology. 2016 Aug 2;87(5):489-96 [PMID: 27371493]
  212. Alzheimers Dement. 2015 Dec;11(12):1407-1416 [PMID: 25936935]
  213. Hum Mol Genet. 2009 Oct 15;18(20):3987-96 [PMID: 19608551]
  214. J Exp Med. 2018 Jun 4;215(6):1627-1647 [PMID: 29643186]
  215. J Exp Med. 2010 May 10;207(5):1067-80 [PMID: 20439540]
  216. Clin Diagn Lab Immunol. 1994 Jan;1(1):109-10 [PMID: 7496909]
  217. J Mol Biol. 2017 Jun 2;429(11):1607-1629 [PMID: 28432014]
  218. Alzheimers Dement. 2017 Apr;13(4):381-387 [PMID: 27520774]
  219. Neurobiol Aging. 1988 Jul-Aug;9(4):339-49 [PMID: 3263583]
  220. J Neurosci. 2017 Apr 26;37(17):4584-4592 [PMID: 28363982]
  221. Arch Neurol. 2006 Apr;63(4):584-8 [PMID: 16606773]
  222. J Immunol. 2003 Jul 15;171(2):594-9 [PMID: 12847223]
  223. Mol Neurodegener. 2019 Jan 21;14(1):5 [PMID: 30665447]
  224. J Clin Invest. 2018 May 1;128(5):2144-2155 [PMID: 29600961]
  225. J Biol Chem. 2015 Oct 23;290(43):26033-42 [PMID: 26374897]
  226. Cell Rep. 2017 Oct 10;21(2):366-380 [PMID: 29020624]
  227. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1977-81 [PMID: 8446617]
  228. Nat Genet. 2019 Mar;51(3):404-413 [PMID: 30617256]
  229. JAMA Neurol. 2013 Jan;70(1):78-84 [PMID: 23318515]
  230. Cell Tissue Res. 2011 Jan;343(1):227-35 [PMID: 20838815]
  231. Proc Natl Acad Sci U S A. 2016 Mar 22;113(12):E1738-46 [PMID: 26884166]
  232. Lancet. 1976 Dec 25;2(8000):1403 [PMID: 63862]
  233. Adv Immunol. 2017;134:137-233 [PMID: 28413021]
  234. FEBS Lett. 1994 May 23;345(1):27-32 [PMID: 8194594]
  235. Cell. 2018 Jun 28;174(1):156-171.e16 [PMID: 29909984]
  236. J Neuroinflammation. 2006 Oct 19;3:29 [PMID: 17052351]
  237. Int J Mol Sci. 2012;13(7):8219-8258 [PMID: 22942700]
  238. Nature. 2011 Aug 31;477(7362):90-4 [PMID: 21886162]
  239. Brain Res. 1991 Feb 8;541(1):163-6 [PMID: 2029618]
  240. J Neurosci. 2003 Sep 17;23(24):8532-8 [PMID: 13679422]
  241. J Clin Invest. 2006 Nov;116(11):3060-9 [PMID: 17080199]
  242. Nat Commun. 2014 Jun 04;5:3917 [PMID: 24894631]
  243. Nat Rev Genet. 2006 Nov;7(11):862-72 [PMID: 17047685]
  244. Neurobiol Aging. 2009 Jan;30(1):1-13 [PMID: 17590238]
  245. Acta Neuropathol. 2012 Jan;123(1):1-11 [PMID: 22101365]
  246. J Neurosci. 2013 Aug 14;33(33):13460-74 [PMID: 23946404]
  247. J Biol Chem. 2015 Oct 23;290(43):26043-50 [PMID: 26374899]
  248. Curr Neurol Neurosci Rep. 2018 Aug 10;18(10):67 [PMID: 30097731]
  249. J Neuroinflammation. 2016 Jan 20;13:17 [PMID: 26792193]
  250. J Exp Med. 2017 Mar 6;214(3):597-607 [PMID: 28209725]
  251. Ann Neurol. 2010 Jun;67(6):715-25 [PMID: 20517933]
  252. Exp Neurol. 1996 Mar;138(1):22-32 [PMID: 8593893]
  253. J Neural Transm (Vienna). 2011 Jan;118(1):23-6 [PMID: 20972807]
  254. Mol Neurodegener. 2017 Oct 16;12(1):74 [PMID: 29037207]
  255. Neuron. 2007 Feb 1;53(3):337-51 [PMID: 17270732]
  256. Neuron. 2017 Feb 8;93(3):533-541.e5 [PMID: 28111080]
  257. Nat Genet. 2009 Oct;41(10):1094-9 [PMID: 19734903]
  258. Annu Rev Immunol. 2014;32:51-82 [PMID: 24313777]
  259. Hum Mol Genet. 2013 Mar 1;22(5):1039-49 [PMID: 23223016]
  260. Nat Immunol. 2017 Jun;18(6):633-641 [PMID: 28459434]
  261. J Mol Neurosci. 2004;23(3):189-204 [PMID: 15181247]
  262. J Exp Med. 2018 Mar 5;215(3):745-760 [PMID: 29321225]
  263. J Exp Med. 2018 Dec 3;215(12):2955-2958 [PMID: 30459159]
  264. Nature. 1995 Feb 9;373(6514):523-7 [PMID: 7845465]
  265. Cell Syst. 2015 Jul 29;1(1):25-36 [PMID: 26236777]
  266. Science. 2005 May 27;308(5726):1314-8 [PMID: 15831717]
  267. Acta Neuropathol. 2016 Jun;131(6):925-33 [PMID: 26754641]
  268. Neuron. 2012 May 24;74(4):691-705 [PMID: 22632727]
  269. Nat Genet. 2000 Aug;25(4):402-5 [PMID: 10932182]
  270. Adv Immunol. 2018;139:1-50 [PMID: 30249333]
  271. Sci Signal. 2010 May 18;3(122):ra38 [PMID: 20484116]
  272. Science. 2014 May 9;344(6184):630-4 [PMID: 24797482]

Grants

  1. /Howard Hughes Medical Institute
  2. RF1 AG051496/NIA NIH HHS
  3. U54 HD090255/NICHD NIH HHS

MeSH Term

Aging
Animals
Complement Activation
Disease Progression
Genetic Predisposition to Disease
Genome-Wide Association Study
Gliosis
Humans
Immunity, Innate
Inflammation
Membrane Glycoproteins
Mice
Mice, Knockout
Mice, Transgenic
Microglia
Models, Immunological
Neurodegenerative Diseases
Protein Aggregation, Pathological
Receptors, Immunologic
Signal Transduction
Transforming Growth Factor beta

Chemicals

Membrane Glycoproteins
Receptors, Immunologic
TREM2 protein, human
Transforming Growth Factor beta
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review
Article has an altmetric score of 51

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