Notably, compared with WT mice, the 5 × FAD mice reported an increase in TLR7, IRF7, IRF9, and Vpreb1/2, which were previously reported to be associated with ABC production,38 and IL33, Lgals9, Cfb, and Tnfsf10, which are reportedly associated with the dysfunction of myeloid cells.39,40 However, Nr4a1, the gatekeeper of B-cell immune tolerance, was decreased in 5 × FAD mice.41 Pathway analysis confirmed that cell senescence, primary immunodeficiency, the B-cell receptor signaling pathway and immunoprotein production were among the highly impacted pathways in the context of AD. Here, VPREB1 is linked to Alzheimer disease.