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Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q

Spurrier, Joshua, Nicholson, LaShae, Fang, Xiaotian T., Stoner, Austin J., Toyonaga, Takuya, Holden, Daniel, Siegert, Timothy R., Laird, William, Allnutt, Mary Alice, Chiasseu, Marius, Brody, A. Harrison, Takahashi, Hideyuki, Nies, Sarah Helena, Pérez-Cañamás, Azucena, Sadasivam, Pragalath, Lee, Supum, Li, Songye, Zhang, Le, Huang, Yiyun H., Carson, Richard E., Cai, Zhengxin, Strittmatter, Stephen M.·2022·Science Translational Medicine
DOI 10.1126/scitranslmed.abi8593PMC PMC9554345
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Abstract

Microglia-mediated synaptic loss contributes to the development of cognitive impairments in Alzheimer’s disease (AD). However, the basis for this immune-mediated attack on synapses remains to be elucidated. Treatment with the metabotropic glutamate receptor 5 (mGluR5) silent allosteric modulator (SAM), BMS-984923, prevents β-amyloid oligomer–induced aberrant synaptic signaling while preserving physiological glutamate response. Here, we show that oral BMS-984923 effectively occupies brain mGluR5 sites visualized by [ 18 F]FPEB positron emission tomography (PET) at doses shown to be safe in rodents and nonhuman primates. In aged mouse models of AD ( APPswe/PS1 Δ E9 overexpressing transgenic and App NL-G-F / hMapt double knock-in), SAM treatment fully restored synaptic density as measured by [ 18 F]SynVesT-1 PET for SV2A and by histology, and the therapeutic benefit persisted after drug washout. Phospho-TAU accumulation in double knock-in mice was also reduced by SAM treatment. Single-nuclei transcriptomics demonstrated that SAM treatment in both models normalized expression patterns to a far greater extent in neurons than glia. Last, treatment prevented synaptic localization of the complement component C1Q and synaptic engulfment in AD mice. Thus, selective modulation of mGluR5 reversed neuronal gene expression changes to protect synapses from damage by microglial mediators in rodents.

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  1. 10.1016/j.biopsych.2017.05.014 · DOI · Paper page
  2. 10.1212/WNL.0000000000006277 · DOI · Paper page
  3. 10.1016/j.cell.2020.05.003 · DOI · Paper page
  4. 10.1016/j.neurobiolaging.2005.09.012 · DOI · Paper page
  5. 10.1002/alz.12097 · DOI · Paper page
  6. 10.1186/s13195-020-00588-4 · DOI · Paper page
  7. 10.1001/jamaneurol.2018.1836 · DOI · Paper page
  8. 10.1093/hmg/ddh019 · DOI · Paper page
  9. 10.2967/jnumed.118.223867 · DOI · Paper page
  10. 10.1007/s11307-020-01567-9 · DOI · Paper page
  11. 10.1038/nn.3178 · DOI
  12. 10.1101/cshperspect.a024075 · DOI · Paper page
  13. 10.1016/j.molcel.2018.10.009 · DOI
  14. 10.1074/jbc.M110.145516 · DOI
  15. 10.1074/jbc.M114.584342 · DOI
  16. 10.1074/jbc.M112.423954 · DOI
  17. 10.1093/brain/awv356 · DOI
  18. 10.1523/JNEUROSCI.0722-17.2017 · DOI · Paper page
  19. 10.1523/JNEUROSCI.0395-10.2010 · DOI · Paper page
  20. 10.1007/s00401-019-02114-9 · DOI
  21. 10.1016/j.biopsych.2017.11.020 · DOI
  22. 10.1242/jcs.111.21.3167 · DOI
  23. 10.1016/j.cell.2010.06.036 · DOI · Paper page
  24. 10.1523/JNEUROSCI.4152-10.2011 · DOI · Paper page
  25. 10.1523/JNEUROSCI.1858-12.2012 · DOI
  26. 10.1074/jbc.M116.738286 · DOI
  27. 10.1074/jbc.M116.720664 · DOI · Paper page
  28. 10.1016/j.celrep.2017.06.023 · DOI
  29. 10.1016/j.celrep.2016.04.077 · DOI
  30. 10.1186/1756-6606-7-40 · DOI
  31. 10.1038/ncomms4374 · DOI
  32. 10.1016/j.neuropharm.2017.03.036 · DOI
  33. 10.1523/JNEUROSCI.2983-18.2018 · DOI · Paper page
  34. 10.1523/JNEUROSCI.1873-18.2018 · DOI · Paper page
  35. Q. Wang, D. M. Walsh, M. J. Rowan, D. J. Selkoe, R. Anwyl, Block of long-term potentiation by naturally secreted and synthetic amyloid beta-peptide in hippocampal slices is mediated via activation of the kinases c-Jun N-terminal kinase, cyclin-dependent kinase 5, and p38 mitogen-activated protein kinase as well as metabotropic glutamate receptor type 5. J. Neurosci. 24, 3370–3378 (2004). · DOI · Paper page
  36. 10.1523/JNEUROSCI.1034-15.2015 · DOI
  37. 10.1186/s13041-015-0111-4 · DOI
  38. 10.1186/1750-1326-9-18 · DOI
  39. 10.1038/s41467-019-09114-z · DOI
  40. 10.1021/acsptsci.0c00013 · DOI
  41. 10.3389/fnagi.2017.00071 · DOI · Paper page
  42. 10.1126/scisignal.abd2494 · DOI
  43. 10.1124/jpet.105.089839 · DOI · Paper page
  44. 10.1124/mol.110.067207 · DOI
  45. 10.1007/s00213-004-1827-5 · DOI
  46. 10.1155/2014/652750 · DOI
  47. 10.1523/JNEUROSCI.17-13-05196.1997 · DOI · Paper page
  48. 10.1523/JNEUROSCI.5716-08.2009 · DOI
  49. 10.1016/j.neuropharm.2010.07.007 · DOI
  50. 10.1124/mol.112.080531 · DOI
  51. 10.1016/j.cell.2007.10.036 · DOI · Paper page
  52. 10.1021/acsmedchemlett.5b00450 · DOI
  53. 10.1016/j.neuron.2020.04.012 · DOI
  54. 10.1101/cshperspect.a006338 · DOI · Paper page
  55. 10.1186/1750-1326-9-48 · DOI
  56. 10.1111/nan.12084 · DOI
  57. 10.1093/bioinformatics/btp101 · DOI · Paper page
  58. 10.1038/s41593-020-0624-8 · DOI · Paper page
  59. 10.1523/JNEUROSCI.3850-15.2016 · DOI
  60. 10.3389/fncel.2019.00063 · DOI
  61. 10.1002/acn3.730 · DOI · Paper page
  62. 10.1016/j.celrep.2018.12.021 · DOI
  63. 10.2967/jnumed.120.249144 · DOI · Paper page
  64. 10.1021/acschemneuro.8b00526 · DOI
  65. 10.1523/JNEUROSCI.4825-12.2013 · DOI · Paper page
  66. J. K. Heiss, J. Barrett, Z. Yu, L. T. Haas, M. A. Kostylev, S. M. Strittmatter, Early activation of experience-independent dendritic spine turnover in a mouse model of Alzheimer’s disease. Cereb. Cortex 27, 3660–3674 (2017).
  67. 10.3233/JAD-180054 · DOI · Paper page
  68. 10.1038/s41586-019-1195-2 · DOI · Paper page
  69. 10.1016/j.brainres.2006.09.106 · DOI
  70. 10.1186/s12864-017-3798-z · DOI
  71. 10.3233/JAD-2010-091594 · DOI · Paper page
  72. 10.3233/JAD-2009-0966 · DOI
  73. 10.1186/s40478-018-0524-2 · DOI · Paper page
  74. 10.1371/journal.pmed.1003012 · DOI
  75. 10.1038/s41598-019-41340-9 · DOI
  76. 10.3233/JAD-131364 · DOI
  77. 10.1016/j.neurobiolaging.2014.01.007 · DOI
  78. 10.1111/j.1471-4159.2011.07447.x · DOI
  79. 10.1016/j.celrep.2019.07.060 · DOI · Paper page
  80. 10.1016/j.neuron.2018.09.017 · DOI
  81. 10.1038/nbt.4096 · DOI · Paper page
  82. 10.1016/j.bmcl.2016.07.065 · DOI
  83. 10.1107/S0108767307043930 · DOI
  84. 10.1023/A:1020884312053 · DOI
  85. 10.1016/j.apradiso.2014.09.006 · DOI
  86. 10.1002/syn.21656 · DOI
  87. 10.1038/sj.jcbfm.9600493 · DOI · Paper page
  88. 10.1038/jcbfm.2009.190 · DOI
  89. 10.3389/neuro.05.001.2008 · DOI
  90. 10.3389/fneur.2018.00516 · DOI
  91. 10.1016/0013-4694(72)90177-0 · DOI
  92. 10.1111/j.1365-2818.2006.01706.x · DOI
  93. H. Wickham in Use R! (Springer International Publishing 2016).

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Metadata

Authors
Spurrier, J., Nicholson, L., Fang, X. T., Stoner, A. J., Toyonaga, T., Holden, D., Siegert, T. R., Laird, W., Allnutt, M. A., Chiasseu, M., Brody, A. H., Takahashi, H., Nies, S. H., Pérez-Cañamás, A., Sadasivam, P., Lee, S., Li, S., Zhang, L., Huang, Y. H., Carson, R. E., Cai, Z., & Strittmatter, S. M.
Affiliations
  • Cellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.
  • Yale PET Center, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06510, USA.
  • Allyx Therapeutics Inc., New Haven, CT 06513, USA.
ORCID
Venue
Science Translational Medicine
Publisher
American Association for the Advancement of Science (AAAS)
Published
2022-06
Volume
14
Issue
647
ISSN
  • 1946-6234
  • 1946-6242
DOI
10.1126/scitranslmed.abi8593
PMC
PMC9554345
Cited by
114
References
27
Language
en

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