Fig. 4
Sulfatide deficiency caused AD-like neuroinflammation, leading to disease-associated microglia and astrocytes signatures. (A) Gene list enrichment analysis using Enrichr for the 72 DEGs shared by both CST cKO and CST KO CNS (listed in Fig. 3C), The top 1 disease reaching a significant difference was Alzheimer’s disease with four AD risk genes: Apoe, Trem2, Cd33, and Mmp12 among the DEGs. (B-E) Linear counts of each of these AD risk genes at different CNS regions/time points for CST cKO and CST KO, compared to their respective controls. (F-H) Three genes previously described as key causal regulators of immune networks for late-onset AD were also among the shared DEGs: Tyrobp, Dock, Fcerg1. (I) Heatmap displaying log2 fold changes of the homeostatic microglia and stage1/2 reactive microglia-specific genes (those included in the Nanostring panel) in the CNS of CST cKO and KO, compared to their respective controls. 0.05 < #p < 0.1, *p < 0.05. (J) Immunofluorescence staining on the hippocampus (CA1 region shown) of CST Cre− and CST Cre+ brain 9 mo post injection using antibodies against typical markers of disease-associated astrocytes: VIM (yellow), GFAP (red) and SerpinA3N (green). Scale bar: 200 μm. (B-I) Heteroscedastic Welch’s t-Test, n = 3–4. *p < 0.05, **p < 0.01, ***p < 0.001. Data represent the mean ± S.E.M