Nova-ST spatial transcriptomics of Lecanamab- and Lecanemab LALA-PG-treated xenotrasplanted human microglia [ST]

We investigated the effect of Lecanemab's Fc effector function on the transcriptomes of human microglia xenotransplanted in a mouse model of AD. We performed Nova-ST spatial transcriptomics analysis on xenografted mice treated with Lecanemab and Lecanemab LALA-PG, a human IgG1 variant designed to abolish Fc-mediated effector functions. We found that treatment with Lecanemab induced phagocytic and lysosomal reprogramming in the microglia surrounding plaques, an effect that was not present upon Lecanemab LALA-PG. Overall design: Human embryonic stem cells (WiCell, #WA09) were differentiated into microglial precursors and grafted into AppNL-G-F Csf1r?FIRE/?FIRE mice. At 4 months, the mice were chronically treated for 8 weeks with 10 mg kg-1 Lecanemab (n=2) or Lecanemab LALA-PG (n=2), dosed weekly intraperitoneally. One day after the final dose, mice were terminally anesthetized and Nova-ST spatial transcriptomics was performed on cryosections of the brains. Only the human (microglial) transcriptomes were analyzed.