scRNA-seq of Lecanamab- and IgG1-treated xenotrasplanted human microglia

We investigated the transcriptomic changes of human microglia xenotransplanted in a mouse model of AD upon treatment with Lecanamab (Lec) compared to control (IgG1). Single-cell RNA sequencing reveals that Lec treatment induces a transcriptional program in microglia that promotes amyloid plaque removal, involving pathways related to phagocytosis, metabolism, antigen presentation, unfolded protein response, and interferon response. Human embryonic stem cells (WiCell, #WA09) were differentiated into microglial precursors and grafted into AppNL-G-F and AppNL-G-F Csf1rΔFIRE/ΔFIRE mice. At 4 months, the mice were chronically treated for 8 weeks with 10 mg kg−1 Lecanemab or IgG1, dosed weekly intraperitoneally. One day after the final dose, mice were terminally anesthetized and human microglia were isolated for single-cell RNA-seq. Only the transcriptomes of the AppNL-G-F Csf1rΔFIRE/ΔFIRE mice were analyzed to evaluate the transcriptional response of human microglia cells to Lecanamab in this model.