Figure 2.

CNS conditioning enhances the recruitment of BM-derived mononuclear phagocytes into the brains of AD transgenic mice. A, Assessment of blood chimerism in brain-protected and unprotected CCR2^+/+GFP → APP^swe/PS1 chimeras. Representative dot plots from individual mice are shown on the left, and the percentages of GFP⁺CD11b⁺Ly-6C^lo and GFP⁺CD11b⁺Ly-6C^hi cells are indicated. SSC, Side scatter. Quantification of Ly-6C^lo- and Ly-6C^hi-expressing GFP-positive cells in the peripheral blood of unprotected and protected CCR2^+/+GFP → APP^swe/PS1 BM chimeras is shown on the right. Data are means ± SEM. At least 5 mice per group were examined. B, Phagocyte engraftment from the hematopoietic compartment requires irradiation of the brains of AD transgenic mice. Ramified GFP- and Iba-1-expressing cells were examined 7 months after BMC transfer. Immunohistochemistry for Iba-1 (blue, left; red, right), Aβ deposits (red), GFP fluorescence (green), and DAPI staining of nuclei (blue) in cortical and hippocampal sections from unprotected and protected CCR2^+/+GFP → APP^swe/PS1 BM chimeras reveals that BM-derived (GFP⁺) Iba-1⁺ mononuclear phagocytes (arrows) are exclusively found in unprotected AD brains, whereas nonirradiated (protected) brains are devoid of parenchymal ramified GFP⁺ cells. Endogenous host microglia are Iba-1⁺GFP⁻ (arrowheads). Scale bars, 30 μm. C–E, Semiquantitative analysis of regional myeloid cell engraftment (GFP⁺Iba-1⁺ cells) in the brain (cortex and hippocampus) (C) and spinal cord (D) of total-body irradiated (unprotected) and brain-shielded (protected) CCR2^+/+GFP → APP^swe/PS1 BM chimeras. Engraftment of BM-derived mononuclear cells strictly depends on irradiation of the nervous tissue in AD transgenic mice. The percentage of plaques surrounded by GFP⁺ mononuclear cells in the conditioned brains is shown in E. Data are means ± SEM from at least three sections per animal and at least 5 mice per group. n.d., Not detectable.