Abstract / Description of output
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.
Original language | English |
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Pages (from-to) | 11159-71 |
Number of pages | 13 |
Journal | Journal of Neuroscience |
Volume | 31 |
Issue number | 31 |
DOIs | |
Publication status | E-pub ahead of print - 3 Aug 2011 |
Keywords / Materials (for Non-textual outputs)
- Alzheimer Disease
- Amyloid beta-Peptides
- Amyloid beta-Protein Precursor
- Animals
- Bone Marrow Transplantation
- CD11b Antigen
- Cell Death
- Cell Proliferation
- Central Nervous System
- Disease Models, Animal
- Gene Expression Regulation
- Green Fluorescent Proteins
- Ki-67 Antigen
- Mice
- Mice, Transgenic
- Microdissection
- Microglia
- Mutation
- Myeloid Cells
- Receptors, CCR2
- Whole-Body Irradiation
- Journal Article
- Research Support, Non-U.S. Gov't