Distinct and Non-Redundant Roles of Microglia and Myeloid Subsets in Mouse Models of Alzheimer's Disease

摘要: Mononuclear phagocytes are important modulators of Alzheimer's disease (AD), but the specific functions resident microglia, bone marrow-derived mononuclear cells, and perivascular macrophages have not been resolved. To elucidate spatiotemporal roles during disease, we targeted myeloid cell subsets from different compartments examined pathogenesis in three mouse models AD (APP(swe/PS1), APP(swe), APP23 mice). We identified chemokine receptor 2 (CCR2)-expressing cells as population that was preferentially recruited to β-amyloid (Aβ) deposits. Unexpectedly, brains with dysfunctional microglia devoid parenchymal did show overt changes plaque pathology Aβ load. In contrast, restriction CCR2 deficiency drastically impaired clearance amplified vascular deposition, while deposition remained unaffected. Together, our data advocate selective CCR2-expressing subsets, which could be specifically modify burden AD.