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Ahmed MM, Johnson NR, Boyd TD, et al. Innate Immune System Activation and Neuroinflammation in Down Syndrome and Neurodegeneration: Therapeutic Targets or Partners?. Front Aging Neurosci. 2021;13:718426doi: 10.3389/fnagi.2021.718426.
Ahmed, M. M., Johnson, N. R., Boyd, T. D., Coughlan, C., Chial, H. J., & Potter, H. (2021). Innate Immune System Activation and Neuroinflammation in Down Syndrome and Neurodegeneration: Therapeutic Targets or Partners?. Frontiers in aging neuroscience, 13718426. https://doi.org/10.3389/fnagi.2021.718426
Ahmed, Md Mahiuddin, et al. "Innate Immune System Activation and Neuroinflammation in Down Syndrome and Neurodegeneration: Therapeutic Targets or Partners?." Frontiers in aging neuroscience vol. 13 (2021): 718426. doi: https://doi.org/10.3389/fnagi.2021.718426
Ahmed MM, Johnson NR, Boyd TD, Coughlan C, Chial HJ, Potter H. Innate Immune System Activation and Neuroinflammation in Down Syndrome and Neurodegeneration: Therapeutic Targets or Partners?. Front Aging Neurosci. 2021 Sep 16;13:718426. doi: 10.3389/fnagi.2021.718426. eCollection 2021. PMID: 34603007; PMCID: PMC8481947.
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Front Aging Neurosci. 2021 Sep 16;13:718426. doi: 10.3389/fnagi.2021.718426. eCollection 2021.

Innate Immune System Activation and Neuroinflammation in Down Syndrome and Neurodegeneration: Therapeutic Targets or Partners?.

Frontiers in aging neuroscience

Md Mahiuddin Ahmed, Noah R Johnson, Timothy D Boyd, Christina Coughlan, Heidi J Chial, Huntington Potter

Affiliations

  1. Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
  2. University of Colorado Alzheimer's and Cognition Center, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
  3. Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
  4. Partner Therapeutics, Inc., Lexington, MA, United States.

PMID: 34603007 PMCID: PMC8481947 DOI: 10.3389/fnagi.2021.718426

Abstract

Innate immune system activation and inflammation are associated with and may contribute to clinical outcomes in people with Down syndrome (DS), neurodegenerative diseases such as Alzheimer's disease (AD), and normal aging. In addition to serving as potential diagnostic biomarkers, innate immune system activation and inflammation may play a contributing or causal role in these conditions, leading to the hypothesis that effective therapies should seek to dampen their effects. However, recent intervention studies with the innate immune system activator granulocyte-macrophage colony-stimulating factor (GM-CSF) in animal models of DS, AD, and normal aging, and in an AD clinical trial suggest that activating the innate immune system and inflammation may instead be therapeutic. We consider evidence that DS, AD, and normal aging are accompanied by innate immune system activation and inflammation and discuss whether and when during the disease process it may be therapeutically beneficial to suppress or promote such activation.

Copyright © 2021 Ahmed, Johnson, Boyd, Coughlan, Chial and Potter.

Keywords: Alzheimer’s disease; Down syndrome; GM-CSF (granulocyte-macrophage colony-stimulating factor); amyloid-β; apolipoprotein E; drug repurposing and discovery; inflammation; innate immune system

Conflict of interest statement

HP and TB are two of the inventors on several U.S. patents owned by the University of South Florida, but not licensed. TB is an employee of Partner Therapeutics. The remaining authors declare that the

References

  1. J Clin Invest. 1994 Aug;94(2):860-9 - PubMed
  2. J Neurosurg. 2009 Jul;111(1):155-63 - PubMed
  3. Biochem Biophys Res Commun. 1993 Apr 30;192(2):359-65 - PubMed
  4. Nat Genet. 2013 Dec;45(12):1452-8 - PubMed
  5. Neurobiol Aging. 2006 Dec;27(12):1763-8 - PubMed
  6. Neurosci Lett. 2008 May 9;436(2):196-200 - PubMed
  7. Neurobiol Aging. 2021 Jul;103:68-77 - PubMed
  8. J Neurosci. 2012 Oct 24;32(43):15181-92 - PubMed
  9. J Neurotrauma. 2014 May 15;31(10):976-83 - PubMed
  10. Eur J Public Health. 2007 Apr;17(2):221-5 - PubMed
  11. Neurobiol Aging. 2000 May-Jun;21(3):383-421 - PubMed
  12. Neurobiol Dis. 2019 Jan;121:327-337 - PubMed
  13. Gene. 2013 Jan 10;512(2):219-25 - PubMed
  14. Alzheimers Dement. 2020 Jul;16(7):1065-1077 - PubMed
  15. Int J Mol Sci. 2020 Aug 03;21(15): - PubMed
  16. Cell. 2017 Jun 15;169(7):1276-1290.e17 - PubMed
  17. Alzheimers Dement (N Y). 2021 Mar 24;7(1):e12158 - PubMed
  18. Nature. 1997 Aug 28;388(6645):878-81 - PubMed
  19. Sci Rep. 2017 Nov 1;7(1):14818 - PubMed
  20. Neuron. 2018 Jun 27;98(6):1141-1154.e7 - PubMed
  21. Brain Res. 1997 Feb 21;749(1):135-8 - PubMed
  22. Clin Dev Immunol. 2013;2013:939786 - PubMed
  23. FASEB J. 2011 May;25(5):1585-95 - PubMed
  24. Neurogenetics. 2007 Aug;8(3):179-88 - PubMed
  25. Am J Med Genet B Neuropsychiatr Genet. 2007 Jun 5;144B(4):469-74 - PubMed
  26. Mol Cell Biol. 2006 May;26(10):3864-74 - PubMed
  27. Am J Med Genet. 1999 Aug 20;88(4):344-7 - PubMed
  28. Int J Mol Sci. 2019 Feb 15;20(4): - PubMed
  29. Hum Mol Genet. 2013 May 1;22(9):1709-24 - PubMed
  30. J Cereb Blood Flow Metab. 2008 Jan;28(1):29-43 - PubMed
  31. J Biol Chem. 1997 Jan 3;272(1):556-62 - PubMed
  32. Neurosci Biobehav Rev. 2019 Mar;98:234-255 - PubMed
  33. J Alzheimers Dis. 2010;21(2):507-18 - PubMed
  34. Graefes Arch Clin Exp Ophthalmol. 2012 May;250(5):699-712 - PubMed
  35. Nature. 2017 Sep 28;549(7673):523-527 - PubMed
  36. Curr Alzheimer Res. 2016;13(1):18-29 - PubMed
  37. Genes (Basel). 2021 Mar 15;12(3): - PubMed
  38. Ann Transl Med. 2019 Nov;7(22):657 - PubMed
  39. Curr Mol Med. 2013 Jan;13(1):24-57 - PubMed
  40. Proc Natl Acad Sci U S A. 2019 Nov 26;116(48):24231-24241 - PubMed
  41. J Neurosci Res. 2013 Jun;91(6):771-9 - PubMed
  42. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3619-23 - PubMed
  43. Proc Natl Acad Sci U S A. 1995 May 23;92(11):4725-7 - PubMed
  44. J Neuroinflammation. 2013 Jul 16;10:84 - PubMed
  45. Alzheimers Dement. 2019 Jun;15(6):776-787 - PubMed
  46. J Alzheimers Dis. 2006;9(3 Suppl):271-6 - PubMed
  47. Cell. 1988 Feb 26;52(4):487-501 - PubMed
  48. Curr Alzheimer Res. 2004 May;1(2):127-33 - PubMed
  49. J Immunother Cancer. 2017 Jul 18;5(1):53 - PubMed
  50. J Neurol Neurosurg Psychiatry. 2003 Sep;74(9):1200-5 - PubMed
  51. Mol Neurobiol. 2019 Feb;56(2):963-975 - PubMed
  52. Front Immunol. 2020 Sep 02;11:2045 - PubMed
  53. Gene. 1997 Sep 1;196(1-2):279-86 - PubMed
  54. J Neurol Sci. 2005 Sep 15;236(1-2):17-24 - PubMed
  55. J Exp Med. 2018 Sep 3;215(9):2235-2245 - PubMed
  56. Biochem Biophys Res Commun. 2012 Apr 6;420(2):404-10 - PubMed
  57. Hum Mol Genet. 2007 Jan 1;16(1):15-23 - PubMed
  58. Neurobiol Aging. 2008 Feb;29(2):194-202 - PubMed
  59. J Biol Chem. 2011 May 13;286(19):17217-26 - PubMed
  60. Brain Disord Ther. 2012;1(1): - PubMed
  61. Trends Neurosci. 1988 Jun;11(6):273-7 - PubMed
  62. Immunity. 2017 Sep 19;47(3):566-581.e9 - PubMed
  63. Neurobiol Aging. 1996 Sep-Oct;17(5):773-80 - PubMed
  64. Nature. 1988 Feb 11;331(6156):528-30 - PubMed
  65. Nature. 2018 Apr;556(7701):332-338 - PubMed
  66. Neurology. 2007 Feb 27;68(9):684-7 - PubMed
  67. Eur J Hum Genet. 2013 Jan;21(1):27-33 - PubMed
  68. Science. 1993 Aug 13;261(5123):921-3 - PubMed
  69. J Neuroimmunol. 2020 Aug 15;345:577272 - PubMed
  70. Neuron. 2009 Oct 15;64(1):110-22 - PubMed
  71. Neuropathol Appl Neurobiol. 2015 Feb;41(1):3-23 - PubMed
  72. Br J Psychiatry. 2000 May;176:468-72 - PubMed
  73. Mol Neurobiol. 2020 Dec;57(12):5352-5361 - PubMed
  74. Lancet Neurol. 2015 Apr;14(4):388-405 - PubMed
  75. J Biol Chem. 1996 May 3;271(18):10602-6 - PubMed
  76. Cytokine. 2015 Oct;75(2):261-71 - PubMed
  77. Biochem Biophys Res Commun. 1984 Aug 16;122(3):1131-5 - PubMed
  78. J Neurochem. 1998 Oct;71(4):1421-8 - PubMed
  79. Ment Retard Dev Disabil Res Rev. 2000;6(2):84-95 - PubMed
  80. JAAD Case Rep. 2019 Apr 05;5(4):365-367 - PubMed
  81. Nat Commun. 2019 Aug 21;10(1):3758 - PubMed
  82. J Neuroinflammation. 2012 Jul 23;9:179 - PubMed
  83. J Exp Med. 2019 Nov 4;216(11):2546-2561 - PubMed
  84. Age (Dordr). 2012 Oct;34(5):1295-308 - PubMed
  85. Brain. 2012 Jul;135(Pt 7):2155-68 - PubMed
  86. J Alzheimers Dis. 2018;62(1):385-397 - PubMed
  87. Acta Neuropathol Commun. 2019 Nov 6;7(1):169 - PubMed
  88. Brain. 1997 Nov;120 ( Pt 11):2083-91 - PubMed
  89. Neurology. 1985 Jul;35(7):957-61 - PubMed
  90. Neurobiol Aging. 2001 Nov-Dec;22(6):903-8 - PubMed
  91. Cell Rep. 2020 Nov 17;33(7):108407 - PubMed
  92. MMWR Morb Mortal Wkly Rep. 2006 Jan 6;54(51):1301-5 - PubMed
  93. Glia. 2015 Jan;63(1):51-65 - PubMed
  94. J Mol Cell Cardiol. 2011 May;50(5):826-40 - PubMed
  95. Am J Pathol. 1994 Nov;145(5):1030-5 - PubMed
  96. Oncotarget. 2017 Sep 19;8(48):84489-84496 - PubMed
  97. Neurobiol Aging. 2015 Sep;36(9):2468-74 - PubMed
  98. Neurology. 1996 Aug;47(2):425-32 - PubMed
  99. Nat Commun. 2019 Oct 18;10(1):4766 - PubMed
  100. Brain. 2019 Oct 1;142(10):3243-3264 - PubMed
  101. J Interferon Cytokine Res. 2015 Aug;35(8):585-99 - PubMed
  102. J Proteome Res. 2012 Feb 3;11(2):1251-63 - PubMed
  103. Genomics. 2007 Dec;90(6):647-60 - PubMed
  104. Neurobiol Aging. 2019 Apr;76:125-132 - PubMed
  105. Int J Alzheimers Dis. 2012;2012:489428 - PubMed
  106. J Biol Chem. 2012 Feb 17;287(8):5253-66 - PubMed
  107. Nat Med. 2018 May;24(5):647-657 - PubMed
  108. Brain. 2020 Dec 1;143(12):3653-3671 - PubMed
  109. Cells. 2020 Sep 21;9(9): - PubMed
  110. J Biol Chem. 2014 Nov 14;289(46):31736-31750 - PubMed
  111. East Asian Arch Psychiatry. 2011 Jun;21(2):79-84 - PubMed
  112. Glia. 2012 Apr;60(4):559-69 - PubMed
  113. Am J Physiol Cell Physiol. 2011 Jan;300(1):C155-63 - PubMed
  114. Neurosci Lett. 2005 Dec 23;390(2):93-7 - PubMed
  115. Neurosci Lett. 1992 Feb 3;135(2):235-8 - PubMed
  116. Ann Neurol. 2002 Aug;52(2):168-74 - PubMed
  117. PLoS Genet. 2014 Sep 04;10(9):e1004606 - PubMed
  118. J Neuroinflammation. 2006 Apr 07;3:10 - PubMed
  119. Stroke. 2007 Apr;38(4):1320-8 - PubMed
  120. Mol Neurodegener. 2018 May 21;13(1):24 - PubMed
  121. Cytokine. 2020 Mar;127:154938 - PubMed
  122. Am J Physiol Regul Integr Comp Physiol. 2011 Jan;300(1):R12-20 - PubMed
  123. Front Mol Neurosci. 2019 May 10;12:125 - PubMed
  124. CNS Neurol Disord Drug Targets. 2016;15(3):329-36 - PubMed
  125. Nature. 2017 Apr 27;544(7651):488-492 - PubMed
  126. Mol Neurodegener. 2018 Mar 1;13(1):11 - PubMed
  127. Ment Retard Dev Disabil Res Rev. 2007;13(3):228-36 - PubMed
  128. Drug Des Devel Ther. 2014 Dec 17;9:103-25 - PubMed
  129. Neuroreport. 1996 Feb 29;7(3):721-5 - PubMed
  130. J Immunol. 2008 Mar 15;180(6):4273-82 - PubMed
  131. Nature. 1994 Nov 3;372(6501):92-4 - PubMed
  132. Neurobiol Aging. 2010 Nov;31(11):1877-84 - PubMed
  133. Nat Genet. 2019 Mar;51(3):414-430 - PubMed
  134. Eur J Hum Genet. 2008 Nov;16(11):1336-40 - PubMed
  135. Acta Neuropathol Commun. 2014 Jun 28;2:75 - PubMed
  136. Alzheimers Dement. 2015 Feb;11(2):216-25.e1 - PubMed
  137. Neurosci Lett. 2011 Jan 7;487(2):144-8 - PubMed
  138. Am J Pathol. 2004 Sep;165(3):937-48 - PubMed
  139. J Neuroimmunol. 2015 Jan 15;278:162-73 - PubMed
  140. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1977-81 - PubMed
  141. CNS Neurol Disord Drug Targets. 2010 Apr;9(2):174-91 - PubMed
  142. Dev Neurobiol. 2019 Jul;79(7):699-710 - PubMed
  143. Biol Sex Differ. 2015 Nov 09;6:24 - PubMed
  144. Neurosci Lett. 1993 Oct 1;160(2):131-4 - PubMed
  145. J Immunol. 2002 Feb 1;168(3):1405-12 - PubMed
  146. PLoS Genet. 2014 Oct 23;10(10):e1004758 - PubMed
  147. Neurobiol Aging. 2007 Aug;28(8):1139-47 - PubMed
  148. Neuron. 2020 Dec 9;108(5):887-904.e12 - PubMed
  149. Curr Protein Pept Sci. 2017;19(2):172-178 - PubMed
  150. Nat Genet. 2007 Jan;39(1):17-23 - PubMed
  151. Neuron. 2017 Dec 6;96(5):1013-1023.e4 - PubMed
  152. J Alzheimers Dis. 2009;17(3):541-51 - PubMed
  153. Front Pediatr. 2020 Feb 27;8:73 - PubMed
  154. Immunol Lett. 2010 Nov 30;134(1):17-25 - PubMed
  155. J Neurochem. 2005 Feb;92(3):546-53 - PubMed
  156. Nat Med. 2007 Apr;13(4):432-8 - PubMed
  157. Am J Med Genet Suppl. 1990;7:31-7 - PubMed
  158. J Clin Med. 2021 Apr 28;10(9): - PubMed
  159. Eur J Neurosci. 2016 Jan;43(1):17-24 - PubMed
  160. Sci Transl Med. 2021 Feb 17;13(581): - PubMed
  161. Mol Psychiatry. 2007 Sep;12(9):870-80 - PubMed
  162. J Alzheimers Dis. 2010;22(4):1305-11 - PubMed
  163. Blood. 1993 Dec 1;82(11):3279-82 - PubMed
  164. J Biol Chem. 2007 Apr 20;282(16):11982-95 - PubMed
  165. Alzheimers Res Ther. 2021 Jan 8;13(1):15 - PubMed
  166. Biochem J. 1995 Mar 1;306 ( Pt 2):599-604 - PubMed
  167. J Neurosci. 2014 May 21;34(21):7281-92 - PubMed
  168. Neurotherapeutics. 2017 Jan;14(1):35-53 - PubMed
  169. J Neuroimmunol. 2018 Jun 15;319:80-92 - PubMed
  170. PLoS One. 2012;7(1):e30525 - PubMed
  171. Neuron. 2017 Dec 6;96(5):1024-1032.e3 - PubMed
  172. Autophagy. 2011 Jul;7(7):788-9 - PubMed
  173. Biogerontology. 2016 Feb;17(1):7-19 - PubMed
  174. J Neurochem. 2009 Aug;110(4):1129-34 - PubMed
  175. J Invest Dermatol. 2010 Jan;130(1):102-12 - PubMed
  176. J Alzheimers Dis. 2017;58(4):1303-1313 - PubMed
  177. J Clin Invest. 2018 Oct 1;128(10):4297-4312 - PubMed
  178. Elife. 2016 Jul 29;5: - PubMed

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