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Impact of peripheral myeloid cells on amyloid-β pathology in Alzheimer’s disease–like mice
Although central nervous system–resident microglia are believed to be ineffective at phagocytosing and clearing amyloid-β (Aβ), a major pathological hallmark of Alzheimer’s disease (AD), it has been suggested that peripheral myeloid cells constitute a heterogeneous cell population with greater Aβ-cl...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612091/ https://www.ncbi.nlm.nih.gov/pubmed/26458768 http://dx.doi.org/10.1084/jem.20150479 |
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author | Prokop, Stefan Miller, Kelly R. Drost, Natalia Handrick, Susann Mathur, Vidhu Luo, Jian Wegner, Anja Wyss-Coray, Tony Heppner, Frank L. |
author_facet | Prokop, Stefan Miller, Kelly R. Drost, Natalia Handrick, Susann Mathur, Vidhu Luo, Jian Wegner, Anja Wyss-Coray, Tony Heppner, Frank L. |
author_sort | Prokop, Stefan |
collection | PubMed |
description | Although central nervous system–resident microglia are believed to be ineffective at phagocytosing and clearing amyloid-β (Aβ), a major pathological hallmark of Alzheimer’s disease (AD), it has been suggested that peripheral myeloid cells constitute a heterogeneous cell population with greater Aβ-clearing capabilities. Here, we demonstrate that the conditional ablation of resident microglia in CD11b-HSVTK (TK) mice is followed by a rapid repopulation of the brain by peripherally derived myeloid cells. We used this system to directly assess the ability of peripheral macrophages to reduce Aβ plaque pathology and therefore depleted and replaced the pool of resident microglia with peripherally derived myeloid cells in Aβ-carrying APPPS1 mice crossed to TK mice (APPPS1;TK). Despite a nearly complete exchange of resident microglia with peripheral myeloid cells, there was no significant change in Aβ burden or APP processing in APPPS1;TK mice. Importantly, however, newly recruited peripheral myeloid cells failed to cluster around Aβ deposits. Even additional anti-Aβ antibody treatment aimed at engaging myeloid cells with amyloid plaques neither directed peripherally derived myeloid cells to amyloid plaques nor altered Aβ burden. These data demonstrate that mere recruitment of peripheral myeloid cells to the brain is insufficient in substantially clearing Aβ burden and suggest that specific additional triggers appear to be required to exploit the full potential of myeloid cell–based therapies for AD. |
format | Online Article Text |
id | pubmed-4612091 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-46120912016-04-19 Impact of peripheral myeloid cells on amyloid-β pathology in Alzheimer’s disease–like mice Prokop, Stefan Miller, Kelly R. Drost, Natalia Handrick, Susann Mathur, Vidhu Luo, Jian Wegner, Anja Wyss-Coray, Tony Heppner, Frank L. J Exp Med Brief Definitive Report Although central nervous system–resident microglia are believed to be ineffective at phagocytosing and clearing amyloid-β (Aβ), a major pathological hallmark of Alzheimer’s disease (AD), it has been suggested that peripheral myeloid cells constitute a heterogeneous cell population with greater Aβ-clearing capabilities. Here, we demonstrate that the conditional ablation of resident microglia in CD11b-HSVTK (TK) mice is followed by a rapid repopulation of the brain by peripherally derived myeloid cells. We used this system to directly assess the ability of peripheral macrophages to reduce Aβ plaque pathology and therefore depleted and replaced the pool of resident microglia with peripherally derived myeloid cells in Aβ-carrying APPPS1 mice crossed to TK mice (APPPS1;TK). Despite a nearly complete exchange of resident microglia with peripheral myeloid cells, there was no significant change in Aβ burden or APP processing in APPPS1;TK mice. Importantly, however, newly recruited peripheral myeloid cells failed to cluster around Aβ deposits. Even additional anti-Aβ antibody treatment aimed at engaging myeloid cells with amyloid plaques neither directed peripherally derived myeloid cells to amyloid plaques nor altered Aβ burden. These data demonstrate that mere recruitment of peripheral myeloid cells to the brain is insufficient in substantially clearing Aβ burden and suggest that specific additional triggers appear to be required to exploit the full potential of myeloid cell–based therapies for AD. The Rockefeller University Press 2015-10-19 /pmc/articles/PMC4612091/ /pubmed/26458768 http://dx.doi.org/10.1084/jem.20150479 Text en © 2015 Prokop et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Brief Definitive Report Prokop, Stefan Miller, Kelly R. Drost, Natalia Handrick, Susann Mathur, Vidhu Luo, Jian Wegner, Anja Wyss-Coray, Tony Heppner, Frank L. Impact of peripheral myeloid cells on amyloid-β pathology in Alzheimer’s disease–like mice |
title | Impact of peripheral myeloid cells on amyloid-β pathology in Alzheimer’s disease–like mice |
title_full | Impact of peripheral myeloid cells on amyloid-β pathology in Alzheimer’s disease–like mice |
title_fullStr | Impact of peripheral myeloid cells on amyloid-β pathology in Alzheimer’s disease–like mice |
title_full_unstemmed | Impact of peripheral myeloid cells on amyloid-β pathology in Alzheimer’s disease–like mice |
title_short | Impact of peripheral myeloid cells on amyloid-β pathology in Alzheimer’s disease–like mice |
title_sort | impact of peripheral myeloid cells on amyloid-β pathology in alzheimer’s disease–like mice |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612091/ https://www.ncbi.nlm.nih.gov/pubmed/26458768 http://dx.doi.org/10.1084/jem.20150479 |
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