microglia clustered around Aβ plaques, with limited neuronal expression. Bulk RNA sequencing of Rag-5xFAD brain tissue demonstrated enrichment of disease-associated microglia (DAM) and senescence-related transcriptional programs. These findings indicate that uPAR marks a subset of plaque-associated glial cells undergoing functional and transcriptional remodeling in AD, independent of peripheral adaptive immune signaling. Collectively, our results identify uPAR as a marker of dysfunctional, DAM-like microglia and implicate it in senescence-associated neuroinflammatory pathways. This work provides a framework for future studies targeting uPAR-expressing glial populations as a potential therapeutic strategy in AD.
Sarko et al. (Sat,) studied this question.