uPAR exhibits age- and region-dependent expression in the brains of mice with Alzheimer’s disease-like pathology
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.
Authors
- Viktoriya Bondarenko
- Daniel C. Shippy
- Kaitlyn M. Marino (ORCID: https://orcid.org/0000-0003-0855-2195)
- Jeanette M. Metzger
- Krishanu Saha (ORCID: https://orcid.org/0000-0003-2837-0858)
- Callista Secker (ORCID: https://orcid.org/0009-0008-8764-1797)
- Marina E. Emborg (ORCID: https://orcid.org/0000-0002-9351-6641)
- Lauren E. Sarko (ORCID: https://orcid.org/0000-0003-0154-8564)
- Mackenzie S. Mnuk (ORCID: https://orcid.org/0009-0002-7914-763X)
- Ella Klaus
- Tyler K. Ulland (ORCID: https://orcid.org/0000-0002-6507-4989)
Institutions
- University of Wisconsin–Madison (US)
- Wisconsin Institutes for Discovery (US)
Publication Details
- Journal
- Brain Research
- Published
- 2026-05-02
- DOI
- https://doi.org/10.1016/j.brainres.2026.150364
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Wisconsin Alumni Research Foundation
- University of Wisconsin-Madison
- National Institutes of Health