Extended Data Fig. 5: Lecanemab affects pathways linked to unfolded protein response, cell metabolism, antigen presentation and interferon response.

a, Weighted gene co-expression network analysis (WGCNA) cluster dendrogram groups genes measured across IgG1- and Lecanemab-treated cells into 14 distinct modules, defined by dendrogram branch cutting. An additional ‘unassigned’ gray module was identified but discarded from subsequent analyses. b, Number of genes belonging to identified WGCNA modules. c, UMAP plots colored by the combined level of expression of each WGCNA module. d, Heatmaps displaying the log fold changes (LFCs) of microglial cell state markers (DAM, HLA, CRM¹⁶) in differential expression between Lecanemab-treated and IgG1-treated microglia. Color intensity reflects the magnitude and direction of differential expression, asterisks denote statistical significance (*: FDR < 0.05, **: FDR < 0.01, ***: FDR < 0.001). e, Cortical tissue domains (TDs) in Lecanemab-treated mice colored based on their relative expression of genes belonging to the salmon (left), greenyellow (middle) and blue (right) modules (purple: low expression, yellow: high expression) and overlayed with plaque ROIs (outlined in cyan). Enrichment scores were obtained using Scanpy’s score_genes() function. Note the significant enrichment of the module in bins close to Aβ plaques, as quantified in Fig. 2b. f, NES of significantly enriched (p.adj < 0.05) weighted gene co-expression network analysis (WGCNA) modules between Lecanemab and Lecanemab LALA-PG-treated TDs in cortical regions, as identified by GSEA with p.adj values indicated. Two-sided p-values were adjusted using the Benjamini–Hochberg (BH) correction (***: p.adj < 0.001). g, Cortical TDs in Lecanemab-treated mice colored based on their relative expression of genes belonging to the red (left) and yellow (right) modules (purple: low expression, yellow: high expression) and overlayed with plaque ROIs (outlined in cyan).