TY - JOUR T1 - Distinct and Non-Redundant Roles of Microglia and Myeloid Subsets in Mouse Models of Alzheimer's Disease JF - The Journal of Neuroscience JO - J. Neurosci. SP - 11159 LP - 11171 DO - 10.1523/JNEUROSCI.6209-10.2011 VL - 31 IS - 31 AU - Alexander Mildner AU - Bernhard Schlevogt AU - Katrin Kierdorf AU - Chotima Böttcher AU - Daniel Erny AU - Markus P. Kummer AU - Michael Quinn AU - Wolfgang Brück AU - Ingo Bechmann AU - Michael T. Heneka AU - Josef Priller AU - Marco Prinz Y1 - 2011/08/03 UR - http://www.jneurosci.org/content/31/31/11159.abstract N2 - 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 (APPswe/PS1, APPswe, 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. ER -