Figure 6.

Immune pathways activated during acute aducanumab treatment are blunted following withdrawal. (A and B) Volcano plots showing DEGs from bulk RNAseq of bulk hemiforebrain tissue after a (A) 15- or (B) 30-wk washout period following four 40 mg/kg doses of aducanumab (Adu) or IgG control. Gene names displayed are the top 15 upregulated and downregulated genes. (C and D) Metascape (C) gene ontology and (D) protein–protein interaction analysis of all genes downregulated with aducanumab treatment at both washout points. (E) Venn diagram showing genes differentially expressed at either week 19 only (early washout), week 34 only (late washout), or at both weeks (shared washout response). (F) Heatmap of selected canonical microglial activation genes curated by Chen and Colonna (2021) from multiple studies of microglial activation, showing differential expression of these genes after two doses of aducanumab (week 3 aducanumab versus week 3 IgG), four doses of aducanumab (week 5 aducanumab versus week 5 IgG), 15-wk washout (week 19 aducanumab versus week 19 IgG), and 30-wk washout (week 34 aducanumab versus week 34 IgG). N = 3–4 mice/sex/treatment/time point, significance at adjusted P val < 0.1 with FDR correction (statistics computed automatically with analysis in edgeR; see Materials and methods for additional details). For heatmaps, *P_val_adj <0.1, **P_val_adj < 0.05; ***P_val_adj < 0.01.