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ApoE facilitates the microglial response to amyloid plaque pathology

One of the hallmarks of Alzheimer’s disease is the presence of extracellular diffuse and fibrillar plaques predominantly consisting of the amyloid-β (Aβ) peptide. Apolipoprotein E (ApoE) influences the deposition of amyloid pathology through affecting the clearance and aggregation of monomeric Aβ in...

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Autores principales: Ulrich, Jason D., Ulland, Tyler K., Mahan, Thomas E., Nyström, Sofie, Nilsson, K. Peter, Song, Wilbur M., Zhou, Yingyue, Reinartz, Mariska, Choi, Seulah, Jiang, Hong, Stewart, Floy R., Anderson, Elise, Wang, Yaming, Colonna, Marco, Holtzman, David M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881464/
https://www.ncbi.nlm.nih.gov/pubmed/29483128
http://dx.doi.org/10.1084/jem.20171265
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author Ulrich, Jason D.
Ulland, Tyler K.
Mahan, Thomas E.
Nyström, Sofie
Nilsson, K. Peter
Song, Wilbur M.
Zhou, Yingyue
Reinartz, Mariska
Choi, Seulah
Jiang, Hong
Stewart, Floy R.
Anderson, Elise
Wang, Yaming
Colonna, Marco
Holtzman, David M.
author_facet Ulrich, Jason D.
Ulland, Tyler K.
Mahan, Thomas E.
Nyström, Sofie
Nilsson, K. Peter
Song, Wilbur M.
Zhou, Yingyue
Reinartz, Mariska
Choi, Seulah
Jiang, Hong
Stewart, Floy R.
Anderson, Elise
Wang, Yaming
Colonna, Marco
Holtzman, David M.
author_sort Ulrich, Jason D.
collection PubMed
description One of the hallmarks of Alzheimer’s disease is the presence of extracellular diffuse and fibrillar plaques predominantly consisting of the amyloid-β (Aβ) peptide. Apolipoprotein E (ApoE) influences the deposition of amyloid pathology through affecting the clearance and aggregation of monomeric Aβ in the brain. In addition to influencing Aβ metabolism, increasing evidence suggests that apoE influences microglial function in neurodegenerative diseases. Here, we characterize the impact that apoE has on amyloid pathology and the innate immune response in APPPS1ΔE9 and APPPS1-21 transgenic mice. We report that Apoe deficiency reduced fibrillar plaque deposition, consistent with previous studies. However, fibrillar plaques in Apoe-deficient mice exhibited a striking reduction in plaque compaction. Hyperspectral fluorescent imaging using luminescent conjugated oligothiophenes identified distinct Aβ morphotypes in Apoe-deficient mice. We also observed a significant reduction in fibrillar plaque–associated microgliosis and activated microglial gene expression in Apoe-deficient mice, along with significant increases in dystrophic neurites around fibrillar plaques. Our results suggest that apoE is critical in stimulating the innate immune response to amyloid pathology.
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spelling pubmed-58814642018-10-02 ApoE facilitates the microglial response to amyloid plaque pathology Ulrich, Jason D. Ulland, Tyler K. Mahan, Thomas E. Nyström, Sofie Nilsson, K. Peter Song, Wilbur M. Zhou, Yingyue Reinartz, Mariska Choi, Seulah Jiang, Hong Stewart, Floy R. Anderson, Elise Wang, Yaming Colonna, Marco Holtzman, David M. J Exp Med Research Articles One of the hallmarks of Alzheimer’s disease is the presence of extracellular diffuse and fibrillar plaques predominantly consisting of the amyloid-β (Aβ) peptide. Apolipoprotein E (ApoE) influences the deposition of amyloid pathology through affecting the clearance and aggregation of monomeric Aβ in the brain. In addition to influencing Aβ metabolism, increasing evidence suggests that apoE influences microglial function in neurodegenerative diseases. Here, we characterize the impact that apoE has on amyloid pathology and the innate immune response in APPPS1ΔE9 and APPPS1-21 transgenic mice. We report that Apoe deficiency reduced fibrillar plaque deposition, consistent with previous studies. However, fibrillar plaques in Apoe-deficient mice exhibited a striking reduction in plaque compaction. Hyperspectral fluorescent imaging using luminescent conjugated oligothiophenes identified distinct Aβ morphotypes in Apoe-deficient mice. We also observed a significant reduction in fibrillar plaque–associated microgliosis and activated microglial gene expression in Apoe-deficient mice, along with significant increases in dystrophic neurites around fibrillar plaques. Our results suggest that apoE is critical in stimulating the innate immune response to amyloid pathology. Rockefeller University Press 2018-04-02 /pmc/articles/PMC5881464/ /pubmed/29483128 http://dx.doi.org/10.1084/jem.20171265 Text en © 2018 Ulrich et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Ulrich, Jason D.
Ulland, Tyler K.
Mahan, Thomas E.
Nyström, Sofie
Nilsson, K. Peter
Song, Wilbur M.
Zhou, Yingyue
Reinartz, Mariska
Choi, Seulah
Jiang, Hong
Stewart, Floy R.
Anderson, Elise
Wang, Yaming
Colonna, Marco
Holtzman, David M.
ApoE facilitates the microglial response to amyloid plaque pathology
title ApoE facilitates the microglial response to amyloid plaque pathology
title_full ApoE facilitates the microglial response to amyloid plaque pathology
title_fullStr ApoE facilitates the microglial response to amyloid plaque pathology
title_full_unstemmed ApoE facilitates the microglial response to amyloid plaque pathology
title_short ApoE facilitates the microglial response to amyloid plaque pathology
title_sort apoe facilitates the microglial response to amyloid plaque pathology
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881464/
https://www.ncbi.nlm.nih.gov/pubmed/29483128
http://dx.doi.org/10.1084/jem.20171265
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