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Parenchymal border macrophages regulate tau pathology and tau-mediated neurodegeneration

Parenchymal border macrophages (PBMs) reside close to the central nervous system parenchyma and regulate CSF flow dynamics. We recently demonstrated that PBMs provide a clearance pathway for amyloid-β peptide, which accumulates in the brain in Alzheimer’s disease (AD). Given the emerging role for PB...

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Autores principales: Drieu, Antoine, Du, Siling, Kipnis, Michal, Bosch, Megan E, Herz, Jasmin, Lee, Choonghee, Jiang, Hong, Manis, Melissa, Ulrich, Jason D, Kipnis, Jonathan, Holtzman, David M, Gratuze, Maud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Life Science Alliance LLC 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10415611/
https://www.ncbi.nlm.nih.gov/pubmed/37562846
http://dx.doi.org/10.26508/lsa.202302087
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author Drieu, Antoine
Du, Siling
Kipnis, Michal
Bosch, Megan E
Herz, Jasmin
Lee, Choonghee
Jiang, Hong
Manis, Melissa
Ulrich, Jason D
Kipnis, Jonathan
Holtzman, David M
Gratuze, Maud
author_facet Drieu, Antoine
Du, Siling
Kipnis, Michal
Bosch, Megan E
Herz, Jasmin
Lee, Choonghee
Jiang, Hong
Manis, Melissa
Ulrich, Jason D
Kipnis, Jonathan
Holtzman, David M
Gratuze, Maud
author_sort Drieu, Antoine
collection PubMed
description Parenchymal border macrophages (PBMs) reside close to the central nervous system parenchyma and regulate CSF flow dynamics. We recently demonstrated that PBMs provide a clearance pathway for amyloid-β peptide, which accumulates in the brain in Alzheimer’s disease (AD). Given the emerging role for PBMs in AD, we explored how tau pathology affects the CSF flow and the PBM populations in the PS19 mouse model of tau pathology. We demonstrated a reduction of CSF flow, and an increase in an MHCII(+)PBM subpopulation in PS19 mice compared with WT littermates. Consequently, we asked whether PBM dysfunction could exacerbate tau pathology and tau-mediated neurodegeneration. Pharmacological depletion of PBMs in PS19 mice led to an increase in tau pathology and tau-dependent neurodegeneration, which was independent of gliosis or aquaporin-4 depolarization, essential for the CSF-ISF exchange. Together, our results identify PBMs as novel cellular regulators of tau pathology and tau-mediated neurodegeneration.
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spelling pubmed-104156112023-08-12 Parenchymal border macrophages regulate tau pathology and tau-mediated neurodegeneration Drieu, Antoine Du, Siling Kipnis, Michal Bosch, Megan E Herz, Jasmin Lee, Choonghee Jiang, Hong Manis, Melissa Ulrich, Jason D Kipnis, Jonathan Holtzman, David M Gratuze, Maud Life Sci Alliance Research Articles Parenchymal border macrophages (PBMs) reside close to the central nervous system parenchyma and regulate CSF flow dynamics. We recently demonstrated that PBMs provide a clearance pathway for amyloid-β peptide, which accumulates in the brain in Alzheimer’s disease (AD). Given the emerging role for PBMs in AD, we explored how tau pathology affects the CSF flow and the PBM populations in the PS19 mouse model of tau pathology. We demonstrated a reduction of CSF flow, and an increase in an MHCII(+)PBM subpopulation in PS19 mice compared with WT littermates. Consequently, we asked whether PBM dysfunction could exacerbate tau pathology and tau-mediated neurodegeneration. Pharmacological depletion of PBMs in PS19 mice led to an increase in tau pathology and tau-dependent neurodegeneration, which was independent of gliosis or aquaporin-4 depolarization, essential for the CSF-ISF exchange. Together, our results identify PBMs as novel cellular regulators of tau pathology and tau-mediated neurodegeneration. Life Science Alliance LLC 2023-08-10 /pmc/articles/PMC10415611/ /pubmed/37562846 http://dx.doi.org/10.26508/lsa.202302087 Text en © 2023 Drieu et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Articles
Drieu, Antoine
Du, Siling
Kipnis, Michal
Bosch, Megan E
Herz, Jasmin
Lee, Choonghee
Jiang, Hong
Manis, Melissa
Ulrich, Jason D
Kipnis, Jonathan
Holtzman, David M
Gratuze, Maud
Parenchymal border macrophages regulate tau pathology and tau-mediated neurodegeneration
title Parenchymal border macrophages regulate tau pathology and tau-mediated neurodegeneration
title_full Parenchymal border macrophages regulate tau pathology and tau-mediated neurodegeneration
title_fullStr Parenchymal border macrophages regulate tau pathology and tau-mediated neurodegeneration
title_full_unstemmed Parenchymal border macrophages regulate tau pathology and tau-mediated neurodegeneration
title_short Parenchymal border macrophages regulate tau pathology and tau-mediated neurodegeneration
title_sort parenchymal border macrophages regulate tau pathology and tau-mediated neurodegeneration
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10415611/
https://www.ncbi.nlm.nih.gov/pubmed/37562846
http://dx.doi.org/10.26508/lsa.202302087
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