Fig. 5

Iba1⁺/TMEM119⁻ cells represent a CD68⁺ macrophage population with peripheral origin highly involved in amyloid-beta phagocytosis. Analysis of CD68 expression in the hippocampus revealed significantly reduced numbers of Iba1⁺/TMEM119⁺/CD68⁺ cells in APP-PS1 and WT animals upon PLX5622 treatment (a). Surprisingly, higher numbers of Iba1⁺/TMEM119⁻/CD68⁺ cells were found in APP-PS1 animals compared to WT, although these numbers were slightly reduced in APP-PS1 animals by PLX5622 treatment (b). Representative image of CD68 expression in Iba1⁺/TMEM119⁻ cells located at sites of plaque in APP-PS1 mice (c). Strong MHCII expression was seen sporadically in Iba1⁺/TMEM119⁻ cells in APP-PS1 mice (d, arrow). Accumulation of CD44 staining (red) was observed extracellularly around amyloid depositions (green) as indicated by the doted ellipse, and CD44 staining was seen on Iba1⁺ cells at sites of plaques (e, insert). Quantification of percentage (%) area of CD44 staining in hippocampal brain regions revealed barely any staining in WT and WT + PLX5622-treated animals; however, in APP-PS1 and APP-PS1 PLX5622-treated mice, significantly higher expression of CD44 was observed compared to WT controls (f). Detailed immunohistochemical analysis revealed increased staining for CD44 at sites of amyloid deposition in areas colonized with Iba1⁺/TMEM119⁻ cells in APP-PS1 and APP-PS1 PLX5622-treated mice (g, arrow). ThioflavinS was used to stain amyloid plaques, and Dapi (blue) was used as nucleus stain. One-way ANOVA with Tukey’s multiple comparison test (a, b, f n = 3/group) was performed. Scale: 50 μm (c, d, e), 20 μm (g)