Display options
Cite
Smit T, Deshayes NAC, Borchelt DR, et al. Reactive astrocytes as treatment targets in Alzheimer's disease-Systematic review of studies using the APPswePS1dE9 mouse model. Glia. 2021;69(8):1852-1881doi: 10.1002/glia.23981.
Smit, T., Deshayes, N. A. C., Borchelt, D. R., Kamphuis, W., Middeldorp, J., & Hol, E. M. (2021). Reactive astrocytes as treatment targets in Alzheimer's disease-Systematic review of studies using the APPswePS1dE9 mouse model. Glia, 69(8), 1852-1881. https://doi.org/10.1002/glia.23981
Smit, Tamar, et al. "Reactive astrocytes as treatment targets in Alzheimer's disease-Systematic review of studies using the APPswePS1dE9 mouse model." Glia vol. 69,8 (2021): 1852-1881. doi: https://doi.org/10.1002/glia.23981
Smit T, Deshayes NAC, Borchelt DR, Kamphuis W, Middeldorp J, Hol EM. Reactive astrocytes as treatment targets in Alzheimer's disease-Systematic review of studies using the APPswePS1dE9 mouse model. Glia. 2021 Aug;69(8):1852-1881. doi: 10.1002/glia.23981. Epub 2021 Feb 25. PMID: 33634529; PMCID: PMC8247905.
Copy Download .nbib Format: NLM
Share it on

Glia. 2021 Aug;69(8):1852-1881. doi: 10.1002/glia.23981. Epub 2021 Feb 25.

Reactive astrocytes as treatment targets in Alzheimer's disease-Systematic review of studies using the APPswePS1dE9 mouse model.

Glia

Tamar Smit, Natasja A C Deshayes, David R Borchelt, Willem Kamphuis, Jinte Middeldorp, Elly M Hol

Affiliations

  1. Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands.
  2. Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands.
  3. Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, Department of Neuroscience, University of Florida College of Medicine, Gainesville, Florida, USA.
  4. Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
  5. Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.

PMID: 33634529 PMCID: PMC8247905 DOI: 10.1002/glia.23981

Abstract

Astrocytes regulate synaptic communication and are essential for proper brain functioning. In Alzheimer's disease (AD) astrocytes become reactive, which is characterized by an increased expression of intermediate filament proteins and cellular hypertrophy. Reactive astrocytes are found in close association with amyloid-beta (Aβ) deposits. Synaptic communication and neuronal network function could be directly modulated by reactive astrocytes, potentially contributing to cognitive decline in AD. In this review, we focus on reactive astrocytes as treatment targets in AD in the APPswePS1dE9 AD mouse model, a widely used model to study amyloidosis and gliosis. We first give an overview of the model; that is, how it was generated, which cells express the transgenes, and the effect of its genetic background on Aβ pathology. Subsequently, to determine whether modifying reactive astrocytes in AD could influence pathogenesis and cognition, we review studies using this mouse model in which interventions were directly targeted at reactive astrocytes or had an indirect effect on reactive astrocytes. Overall, studies specifically targeting astrocytes to reduce astrogliosis showed beneficial effects on cognition, which indicates that targeting astrocytes should be included in developing novel therapies for AD.

© 2021 The Authors. GLIA published by Wiley Periodicals LLC.

Keywords: AD mouse model; APPswePS1dE9; Alzheimer's disease; amyloid-beta; reactive astrocytes

References

  1. Neuron. 2019 Feb 6;101(3):351-352 - PubMed
  2. J Neurol Sci. 2007 Sep 15;260(1-2):204-13 - PubMed
  3. J Biol Chem. 2012 Feb 24;287(9):6912-27 - PubMed
  4. J Neurosci. 2015 Feb 11;35(6):2817-29 - PubMed
  5. Physiology (Bethesda). 2008 Aug;23:194-204 - PubMed
  6. Trends Neurosci. 2008 Dec;31(12):653-9 - PubMed
  7. Alzheimers Res Ther. 2019 May 13;11(1):44 - PubMed
  8. J Cereb Blood Flow Metab. 2008 Mar;28(3):468-81 - PubMed
  9. Cell. 2016 Jun 30;166(1):193-208 - PubMed
  10. J Alzheimers Dis. 2017;58(3):775-787 - PubMed
  11. Nat Genet. 2013 Dec;45(12):1452-8 - PubMed
  12. Neurobiol Aging. 2014 Dec;35(12):2746-2760 - PubMed
  13. Brain. 2006 Nov;129(Pt 11):3006-19 - PubMed
  14. J Neurosci. 2006 May 17;26(20):5438-47 - PubMed
  15. Neurobiol Aging. 2009 Nov;30(11):1756-76 - PubMed
  16. Cell Signal. 2016 Jan;28(1):1-11 - PubMed
  17. Nature. 1991 Oct 31;353(6347):844-6 - PubMed
  18. Front Neurosci. 2019 Feb 28;13:164 - PubMed
  19. EMBO J. 2011 Jun 1;30(11):2266-80 - PubMed
  20. Eur J Hum Genet. 2000 Apr;8(4):259-66 - PubMed
  21. Brain. 2015 Jul;138(Pt 7):2005-19 - PubMed
  22. Neurotox Res. 2016 Feb;29(2):256-66 - PubMed
  23. Nature. 2000 Sep 7;407(6800):48-54 - PubMed
  24. Physiol Rev. 2018 Jan 1;98(1):239-389 - PubMed
  25. J Neuropathol Exp Neurol. 2012 May;71(5):362-81 - PubMed
  26. J Physiol. 2013 Nov 15;591(22):5599-609 - PubMed
  27. Nature. 1991 Feb 21;349(6311):704-6 - PubMed
  28. Proc Natl Acad Sci U S A. 2013 Jul 2;110(27):E2518-27 - PubMed
  29. Neurochem Res. 2020 Jun;45(6):1298-1305 - PubMed
  30. Mol Neurobiol. 2017 Dec;54(10):7964-7978 - PubMed
  31. Brain Res Mol Brain Res. 2004 May 19;124(2):114-23 - PubMed
  32. PLoS One. 2017 Jan 19;12(1):e0170450 - PubMed
  33. J Neurosci. 2014 Sep 3;34(36):11929-47 - PubMed
  34. Mol Cell Biol. 2020 Mar 30;40(8): - PubMed
  35. Glia. 2015 Jun;63(6):1036-56 - PubMed
  36. Neuron. 1996 Nov;17(5):1005-13 - PubMed
  37. Acta Neuropathol. 1991;82(4):239-59 - PubMed
  38. Neurochem Int. 2012 Oct;61(5):739-48 - PubMed
  39. J Neurosci. 2009 Oct 14;29(41):13042-52 - PubMed
  40. J Alzheimers Dis. 2017;57(4):1171-1183 - PubMed
  41. Nat Neurosci. 2020 Dec;23(12):1555-1566 - PubMed
  42. Nat Med. 2020 Jan;26(1):131-142 - PubMed
  43. Glia. 2012 Aug;60(8):1192-202 - PubMed
  44. Cell Death Differ. 2015 Jun;22(6):921-34 - PubMed
  45. Nature. 2017 Jan 26;541(7638):481-487 - PubMed
  46. EMBO Mol Med. 2016 Jun 01;8(6):595-608 - PubMed
  47. Acta Neuropathol Commun. 2018 Oct 16;6(1):104 - PubMed
  48. Life Sci. 2018 Sep 1;208:175-191 - PubMed
  49. Brain Sci. 2020 Mar 13;10(3): - PubMed
  50. Neurobiol Aging. 2010 Jul;31(7):1173-87 - PubMed
  51. Exp Gerontol. 2000 Jul;35(4):453-60 - PubMed
  52. Nat Rev Neurosci. 2005 Aug;6(8):626-40 - PubMed
  53. Nat Commun. 2020 Mar 5;11(1):1220 - PubMed
  54. Nature. 1992 Dec 17;360(6405):672-4 - PubMed
  55. Brain Res Bull. 2018 Jan;136:139-156 - PubMed
  56. J Biol Chem. 1999 Mar 19;274(12):7615-8 - PubMed
  57. J Cell Biol. 2007 Dec 3;179(5):951-63 - PubMed
  58. J Neurochem. 2013 Jul;126(2):183-90 - PubMed
  59. J Neurochem. 2011 Jan;116(1):43-52 - PubMed
  60. J Alzheimers Dis. 2009;18(1):177-89 - PubMed
  61. Neurobiol Dis. 2007 Oct;28(1):3-15 - PubMed
  62. Brain Res. 2019 Sep 15;1719:1-10 - PubMed
  63. J Neuroinflammation. 2020 Mar 20;17(1):91 - PubMed
  64. Behav Brain Res. 2019 Aug 5;368:111910 - PubMed
  65. J Alzheimers Dis. 2020;73(4):1541-1554 - PubMed
  66. Science. 2002 Jul 19;297(5580):353-6 - PubMed
  67. Mol Neurodegener. 2017 Dec 22;12(1):89 - PubMed
  68. J Biol Chem. 2006 May 26;281(21):14776-86 - PubMed
  69. Science. 1982 Mar 5;215(4537):1237-9 - PubMed
  70. Nature. 1995 Aug 31;376(6543):775-8 - PubMed
  71. Biochem Pharmacol. 2010 Jan 15;79(2):77-89 - PubMed
  72. Neurosci Bull. 2011 Aug;27(4):221-32 - PubMed
  73. Brain. 2013 May;136(Pt 5):1415-31 - PubMed
  74. Neuropharmacology. 2019 Jan;144:377-387 - PubMed
  75. Science. 2016 May 6;352(6286):712-716 - PubMed
  76. J Immunol. 1995 Sep 1;155(5):2303-5 - PubMed
  77. J Neurol Sci. 2021 Feb 15;421:117253 - PubMed
  78. Glia. 2009 Feb;57(3):244-57 - PubMed
  79. Pathol Int. 1998 May;48(5):332-40 - PubMed
  80. Mol Cell Neurosci. 2016 Jun;73:13-31 - PubMed
  81. J Biol Chem. 2004 Jun 4;279(23):24601-11 - PubMed
  82. Brain. 2018 Jul 1;141(7):1917-1933 - PubMed
  83. Nature. 2002 Apr 4;416(6880):535-9 - PubMed
  84. Brain Res Bull. 2012 May 1;88(1):3-12 - PubMed
  85. Nat Med. 1998 Apr;4(4):452-5 - PubMed
  86. Nat Med. 1995 Dec;1(12):1291-6 - PubMed
  87. Prog Neurobiol. 2013 Jul-Aug;106-107:33-54 - PubMed
  88. Curr Alzheimer Res. 2010 Mar;7(2):126-33 - PubMed
  89. Ann N Y Acad Sci. 1996 Jan 17;777:57-64 - PubMed
  90. Brain Res. 1999 Sep 4;840(1-2):23-35 - PubMed
  91. Neurobiol Dis. 2006 Dec;24(3):516-24 - PubMed
  92. Neuropathol Appl Neurobiol. 2001 Jun;27(3):189-96 - PubMed
  93. Neurochem Int. 1994 Jul;25(1):73-80 - PubMed
  94. J Biol Chem. 2007 Aug 3;282(31):22707-20 - PubMed
  95. Nat Neurosci. 2010 May;13(5):584-91 - PubMed
  96. Nature. 1998 Jan 22;391(6665):387-90 - PubMed
  97. Neuropharmacology. 2013 Jul;70:200-10 - PubMed
  98. Neuron. 1996 Oct;17(4):607-15 - PubMed
  99. Glia. 1999 Feb 15;25(4):390-403 - PubMed
  100. Curr Alzheimer Res. 2018;15(12):1123-1135 - PubMed
  101. Neuron. 2019 Feb 6;101(3):399-411.e5 - PubMed
  102. Mol Neurodegener. 2020 Nov 27;15(1):71 - PubMed
  103. Nat Genet. 1992 Aug;1(5):345-7 - PubMed
  104. Nat Commun. 2014 Nov 19;5:5422 - PubMed
  105. Semin Cell Dev Biol. 2009 Apr;20(2):183-90 - PubMed
  106. Neuron. 1991 Apr;6(4):487-98 - PubMed
  107. Autophagy. 2020 Jan;16(1):52-69 - PubMed
  108. Acta Neuropathol. 2016 Mar;131(3):323-45 - PubMed
  109. J Biol Chem. 2020 Nov 27;295(48):16251-16266 - PubMed
  110. FEBS Lett. 2013 Jun 27;587(13):2046-54 - PubMed
  111. Proc Natl Acad Sci U S A. 2011 Aug 23;108(34):E559-68 - PubMed
  112. Int J Mol Med. 2017 Jan;39(1):21-30 - PubMed
  113. EMBO J. 2017 Sep 1;36(17):2473-2487 - PubMed
  114. Mt Sinai J Med. 2010 Jan-Feb;77(1):69-81 - PubMed
  115. Nat Rev Neurosci. 2015 May;16(5):249-63 - PubMed
  116. J Neurosci. 2009 Mar 11;29(10):3276-87 - PubMed
  117. Biomol Eng. 2001 Jun;17(6):157-65 - PubMed
  118. Prog Neurobiol. 2016 Sep;144:121-41 - PubMed
  119. Neuron. 1997 Oct;19(4):939-45 - PubMed
  120. Neuron. 2016 Jan 6;89(1):37-53 - PubMed
  121. Nat Rev Neurol. 2018 Jun;14(6):351-362 - PubMed
  122. J Neurosci. 2006 Dec 20;26(51):13279-86 - PubMed
  123. J Alzheimers Dis. 2013;33(4):941-59 - PubMed
  124. Curr Opin Cell Biol. 2015 Feb;32:121-30 - PubMed
  125. Science. 1995 Aug 18;269(5226):973-7 - PubMed
  126. Neuropharmacology. 2014 Apr;79:180-9 - PubMed
  127. Neurobiol Aging. 2014 Jan;35(1):1-14 - PubMed
  128. Neurobiol Aging. 2010 Apr;31(4):578-90 - PubMed
  129. Neuroscience. 2009 Jun 16;161(1):53-8 - PubMed
  130. Hum Mol Genet. 2001 Oct 15;10(22):2525-37 - PubMed
  131. J Neurosci. 2002 Jan 1;22(1):183-92 - PubMed
  132. Neurochem Res. 2017 Sep;42(9):2519-2536 - PubMed
  133. Brain Res. 2017 Feb 1;1656:98-106 - PubMed
  134. Trends Neurosci. 2012 Aug;35(8):497-506 - PubMed
  135. Int J Alzheimers Dis. 2011;2011:517160 - PubMed
  136. Science. 2008 Dec 5;322(5907):1551-5 - PubMed
  137. Glia. 2019 May;67(5):915-934 - PubMed
  138. Neuropharmacology. 2020 Jan 1;162:107813 - PubMed
  139. Sci Rep. 2017 Sep 5;7(1):10411 - PubMed
  140. Nature. 2009 Feb 19;457(7232):981-9 - PubMed
  141. ACS Chem Neurosci. 2019 Dec 18;10(12):4787-4799 - PubMed
  142. Proc Natl Acad Sci U S A. 2018 Feb 20;115(8):E1896-E1905 - PubMed
  143. FASEB J. 2013 Jan;27(1):187-98 - PubMed
  144. Neuroreport. 1995 Dec 29;7(1):297-301 - PubMed
  145. Dev Cell. 2002 Jul;3(1):85-97 - PubMed
  146. Science. 2009 Feb 27;323(5918):1211-5 - PubMed
  147. Neurodegener Dis. 2014;13(2-3):61-3 - PubMed
  148. Nat Neurosci. 2021 Mar;24(3):312-325 - PubMed
  149. PLoS One. 2010 Dec 02;5(12):e14203 - PubMed
  150. Eur J Neurosci. 2006 Apr;23(8):2035-47 - PubMed
  151. Brain. 2015 Aug;138(Pt 8):2399-422 - PubMed
  152. Prog Neurobiol. 2017 Sep;156:189-213 - PubMed
  153. Nat Neurosci. 2014 May;17(5):661-3 - PubMed
  154. J Neuroinflammation. 2011 Aug 09;8:92 - PubMed
  155. PLoS One. 2015 May 01;10(5):e0125897 - PubMed
  156. Cell. 2016 Feb 11;164(4):603-15 - PubMed
  157. Neurobiol Aging. 2014 Mar;35(3):492-510 - PubMed
  158. Neurobiol Aging. 2017 Jul;55:115-122 - PubMed
  159. Glia. 2013 Oct;61(10):1673-86 - PubMed
  160. Sci Adv. 2019 Mar 20;5(3):eaav0316 - PubMed
  161. Neurobiol Aging. 2013 May;34(5):1328-42 - PubMed
  162. Mol Neurobiol. 2015 Feb;51(1):300-12 - PubMed
  163. J Neurosci. 2008 Nov 5;28(45):11622-34 - PubMed
  164. Nat Commun. 2013;4:1495 - PubMed
  165. J Neuroimmunol. 1989 Oct;24(3):173-82 - PubMed
  166. EMBO Mol Med. 2019 Feb;11(2): - PubMed
  167. J Alzheimers Dis. 2020;74(1):173-187 - PubMed
  168. Aging Cell. 2020 Oct 14;:e13246 - PubMed
  169. Acta Neuropathol. 2008 Jan;115(1):5-38 - PubMed
  170. Cell Physiol Biochem. 2007;20(6):947-56 - PubMed
  171. Front Mol Neurosci. 2019 Feb 06;12:23 - PubMed
  172. Eur J Neurosci. 1998 Jun;10(6):2129-42 - PubMed
  173. Cell Death Differ. 2020 Jan;27(1):192-209 - PubMed
  174. Glia. 2017 Oct;65(10):1607-1625 - PubMed
  175. J Clin Invest. 2014 Mar;124(3):1000-12 - PubMed
  176. Trends Neurosci. 1997 Apr;20(4):154-9 - PubMed
  177. Brain Pathol. 2016 Jan;26(1):62-74 - PubMed
  178. J Neurosci. 2007 Apr 4;27(14):3712-21 - PubMed
  179. Curr Alzheimer Res. 2009 Dec;6(6):531-40 - PubMed
  180. J Biol Chem. 1999 Mar 5;274(10):6483-92 - PubMed
  181. Neuron. 2014 Feb 19;81(4):728-39 - PubMed
  182. Glia. 2020 Feb;68(2):215-226 - PubMed
  183. Glia. 2019 Dec;67(12):2221-2247 - PubMed
  184. Cell Death Differ. 2016 Oct;23(10):1691-701 - PubMed
  185. J Psychiatry Neurosci. 2017 Jan;42(1):59-69 - PubMed
  186. Acta Neuropathol Commun. 2014 Jun 29;2:76 - PubMed
  187. PLoS One. 2009 Jun 24;4(6):e6033 - PubMed
  188. Glia. 2014 Dec;62(12):2022-33 - PubMed
  189. Nat Med. 1997 Jul;3(7):756-60 - PubMed
  190. Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):775-9 - PubMed
  191. Trends Pharmacol Sci. 1991 Oct;12(10):383-8 - PubMed
  192. Nature. 2018 Nov;563(7729):72-78 - PubMed
  193. Purinergic Signal. 2009 Jun;5(2):129-37 - PubMed
  194. Brain. 2019 Jan 1;143(1):336-358 - PubMed
  195. Nat Rev Neurosci. 2010 Feb;11(2):87-99 - PubMed
  196. J Neurosci. 2009 Mar 18;29(11):3453-62 - PubMed
  197. Nature. 1999 Apr 8;398(6727):513-7 - PubMed
  198. Trends Neurosci. 2011 Feb;34(2):76-87 - PubMed
  199. Neuron. 2008 Jul 31;59(2):214-25 - PubMed
  200. Neurobiol Dis. 2017 May;101:1-7 - PubMed
  201. Glia. 2012 Apr;60(4):615-29 - PubMed
  202. Cell. 2017 Jul 27;170(3):443-456.e14 - PubMed
  203. J Neuroinflammation. 2019 Mar 14;16(1):62 - PubMed
  204. J Alzheimers Dis. 2013;34(4):873-85 - PubMed
  205. J Neuroinflammation. 2008 May 29;5:23 - PubMed
  206. J Neuroinflammation. 2016 Apr 27;13(1):92 - PubMed
  207. EMBO Rep. 2006 Jul;7(7):739-45 - PubMed
  208. PLoS One. 2013 Nov 20;8(11):e80706 - PubMed
  209. Glia. 2021 Aug;69(8):1852-1881 - PubMed
  210. Neurosci Lett. 1997 May 30;228(1):17-20 - PubMed
  211. Nature. 1995 Jun 29;375(6534):754-60 - PubMed
  212. Science. 1998 Dec 11;282(5396):2085-8 - PubMed
  213. J Neurosci. 2019 Jan 23;39(4):758-772 - PubMed
  214. Nat Med. 2014 Aug;20(8):886-96 - PubMed
  215. Trends Neurosci. 1999 May;22(5):208-15 - PubMed
  216. J Neurosci. 2014 Feb 12;34(7):2674-83 - PubMed
  217. Nat Neurosci. 2020 Jun;23(6):701-706 - PubMed
  218. Hum Mol Genet. 2004 Jan 15;13(2):159-70 - PubMed
  219. Neurobiol Dis. 2021 Jan;148:105219 - PubMed
  220. Neuron. 2003 Apr 10;38(1):9-12 - PubMed
  221. Neuron. 2017 Dec 6;96(5):1024-1032.e3 - PubMed
  222. Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11172-7 - PubMed
  223. Am J Pathol. 1998 Jan;152(1):251-9 - PubMed
  224. J Biol Chem. 2010 Dec 31;285(53):41443-54 - PubMed
  225. Nat Neurosci. 2015 Nov;18(11):1539-1545 - PubMed
  226. Genet Anal. 1996 Dec;13(6):159-63 - PubMed
  227. Neuropharmacology. 2016 Jun;105:561-576 - PubMed

Publication Types

Grant support