Fig 1: Stat3 deletion triggers a phenotypical switch in reactive astrocytes A, BQuantitative PCR from cortex of APP/PS1-Stat3KO compared to APP/PS1-Stat3WT mice revealed lower expression of “A1” markers Amigo2 and C3, whereas Ggta1 remained unchanged. In turn, the “A2” marker Tm4sf1 was upregulated and there was a nonsignificant trend for a higher expression of B3gnt5 (n = 6 mice (three females and three males) per group; age, 8 months; *P < 0.05, Mann–Whitney test).C–FConfirming lower expression of the “A1” marker C3d, Western blot analysis indicated lower protein levels of C3d in APP/PS1-Stat3KO. Immunohistochemistry using an antibody against C3d revealed that lower expression of C3d particularly occurred in peri-plaque reactive astrocytes (arrows indicate C3d and GFAP colocalization; arrowheads indicate plaques visualized with methoxy-XO4; scale bars, 50 µm; APP/PS1-Stat3WT, n = 6 (two females and four males) mice; APP/PS1-Stat3KO, n = 6 (three females and three males) mice; age, 8 months; *P < 0.05, Mann–Whitney test).GWhole-brain levels of the pro-inflammatory cytokines IL-1ß and TNF-a were significantly reduced in APP/PS1-Stat3KO mice (Mann–Whitney test), whereas no changes were seen for IL-10 (APP/PS1-Stat3WT, n = 13 (six females and seven males) mice; APP/PS1-Stat3KO, n = 13 (eight females and five males) mice; age, 11 months; *P < 0.05, Mann–Whitney test).HThese changes were paralleled by a decrease in the area covered by dystrophic neurites in APP/PS1-Stat3KO compared to APP/PS1-Stat3WT mice, as assessed by LAMP1 staining (*P < 0.05, Mann–Whitney test; n = 10 male mice for both groups; age, 8 months; scale bars, 300 µm).Data information: Data are represented as mean ± SEM.