View in EDS

Distinct and non-redundant roles of microglia and myeloid subsets in mouse models of Alzheimer's disease.

Saved in:
Bibliographic Details
Title: Distinct and non-redundant roles of microglia and myeloid subsets in mouse models of Alzheimer's disease.
Authors: Mildner, Alexander, Schlevogt, Bernhard, Kierdorf, Katrin, Böttcher, Chotima, Erny, Daniel, Kummer, Markus P, Quinn, Michael, Brück, Wolfgang, Bechmann, Ingo, HENEKA, Michael, Priller, Josef, Prinz, Marco
Source: Journal of Neuroscience, 31 (31), 11159 - 11171 (2011-08-03)
Publisher Information: Society for Neuroscience
Publication Year: 2011
Collection: University of Luxembourg: ORBilu - Open Repository and Bibliography
Subject Terms: Amyloid beta-Peptides, Amyloid beta-Protein Precursor, CD11b Antigen, Ccr2 protein, mouse, Ki-67 Antigen, Receptors, CCR2, enhanced green fluorescent protein, Green Fluorescent Proteins, Alzheimer Disease/genetics, Alzheimer Disease/pathology, Alzheimer Disease/surgery, Amyloid beta-Peptides/metabolism, Amyloid beta-Protein Precursor/genetics, Animals, Bone Marrow Transplantation/methods, CD11b Antigen/metabolism, Cell Death/radiation effects, Cell Proliferation/radiation effects, Central Nervous System/pathology, Disease Models, Animal, Gene Expression Regulation, Green Fluorescent Proteins/genetics, Ki-67 Antigen/metabolism, Mice, Transgenic, Microdissection/methods, Microglia/physiology
Description: peer reviewed ; Mononuclear phagocytes are important modulators of Alzheimer's disease (AD), but the specific functions of resident microglia, bone marrow-derived mononuclear cells, and perivascular macrophages have not been resolved. To elucidate the spatiotemporal roles of mononuclear phagocytes during disease, we targeted myeloid cell subsets from different compartments and examined disease pathogenesis in three different mouse models of AD (APP(swe/PS1), APP(swe), and APP23 mice). We identified chemokine receptor 2 (CCR2)-expressing myeloid cells as the population that was preferentially recruited to β-amyloid (Aβ) deposits. Unexpectedly, AD brains with dysfunctional microglia and devoid of parenchymal bone marrow-derived phagocytes did not show overt changes in plaque pathology and Aβ load. In contrast, restriction of CCR2 deficiency to perivascular myeloid cells drastically impaired β-amyloid clearance and amplified vascular Aβ deposition, while parenchymal plaque deposition remained unaffected. Together, our data advocate selective functions of CCR2-expressing myeloid subsets, which could be targeted specifically to modify disease burden in AD.
Document Type: article in journal/newspaper
Language: English
ISSN: 0270-6474
1529-2401
Relation: urn:issn:0270-6474; urn:issn:1529-2401; https://orbilu.uni.lu/handle/10993/60971; info:hdl:10993/60971; https://orbilu.uni.lu/bitstream/10993/60971/1/11159.full.pdf; info:pmid:21813677; wos:000293459400008
DOI: 10.1523/JNEUROSCI.6209-10.2011
Availability: https://orbilu.uni.lu/handle/10993/60971
https://orbilu.uni.lu/bitstream/10993/60971/1/11159.full.pdf
https://doi.org/10.1523/JNEUROSCI.6209-10.2011
Rights: open access ; http://purl.org/coar/access_right/c_abf2 ; info:eu-repo/semantics/openAccess
Accession Number: edsbas.E9940E2B
Database: BASE
Description
Abstract:peer reviewed ; Mononuclear phagocytes are important modulators of Alzheimer's disease (AD), but the specific functions of resident microglia, bone marrow-derived mononuclear cells, and perivascular macrophages have not been resolved. To elucidate the spatiotemporal roles of mononuclear phagocytes during disease, we targeted myeloid cell subsets from different compartments and examined disease pathogenesis in three different mouse models of AD (APP(swe/PS1), APP(swe), and APP23 mice). We identified chemokine receptor 2 (CCR2)-expressing myeloid cells as the population that was preferentially recruited to β-amyloid (Aβ) deposits. Unexpectedly, AD brains with dysfunctional microglia and devoid of parenchymal bone marrow-derived phagocytes did not show overt changes in plaque pathology and Aβ load. In contrast, restriction of CCR2 deficiency to perivascular myeloid cells drastically impaired β-amyloid clearance and amplified vascular Aβ deposition, while parenchymal plaque deposition remained unaffected. Together, our data advocate selective functions of CCR2-expressing myeloid subsets, which could be targeted specifically to modify disease burden in AD.
ISSN:02706474
15292401
DOI:10.1523/JNEUROSCI.6209-10.2011