Journal
JOURNAL OF NEUROSCIENCE
Volume 31, Issue 31, Pages 11159-11171Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.6209-10.2011
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Funding
- German Research Council (DFG) [PR 577/5-1, FOR1336]
- Bundesministerium fuer Bildung und Forschung
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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 beta-amyloid (A beta) deposits. Unexpectedly, AD brains with dysfunctional microglia and devoid of parenchymal bone marrow-derived phagocytes did not show overt changes in plaque pathology and A beta load. In contrast, restriction of CCR2 deficiency to perivascular myeloid cells drastically impaired beta-amyloid clearance and amplified vascular A beta 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.
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