Prokop, S;
Miller, KR;
Drost, N;
Handrick, S;
Mathur, V;
Luo, J;
Wegner, A;
... Heppner, FL; + view all
(2015)
Impact of peripheral myeloid cells on amyloid-β pathology in Alzheimer's disease-like mice.
Journal of Experimental Medicine
, 212
(11)
pp. 1811-1818.
10.1084/jem.20150479.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Impact of peripheral myeloid cells on amyloid-β pathology in Alzheimer's disease-like mice. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1084/jem.20150479 |
| Publisher version: | http://dx.doi.org/ 10.1084/jem.20150479 |
| Language: | English |
| Additional information: | Copyright © 2017 JEM by The Rockefeller University Press This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Alzheimer Disease, Amyloid beta-Peptides, Animals, Cell Movement, Disease Models, Animal, Ganciclovir, Male, Mice, Microglia, Myeloid Cells, Vaccination |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1555037 |
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