Mature tau pathology is not improved by interfering with interleukin-1 receptor signaling in two mouse models of tauopathy

Dylan J Finneran, Brianna M Jackman, Taylor Desjarlais, Alayna Henry, Ahlam S Soliman, Patricia C Muskus, Rama Shankar, Bin Chen, Kevin R Nash, Dave Morgan and Marcia N Gordon

PLOS ONE, 2025, vol. 20, issue 11, 1-19

Abstract: Prior work suggests that the cytokine interleukin-1β (IL-1β) may be a key regulator of tau pathology in the presence of amyloidosis. Here, we tested the possible benefits of interleukin-1 receptor antagonist (IL-1RA) gene therapy in two mouse models of tauopathy. We performed intracranial injections in the rTg4510 model, achieving approximately 300-fold over-expression in the hippocampus, and systemic injections in the PS19 model, resulting in approximately 10-fold over-expression. In neither model did we find substantial treatment effects with IL-1RA over-expression. We found large increases in Il1b gene expression in these mouse models, but considerably smaller increases in IL-1β protein. These data suggest that interleukin-1 receptor antagonist may not be a viable therapeutic strategy for pure tauopathies but cannot rule out possible benefits in amyloid-enhanced tauopathy, which appear to have larger elevations of IL-1β.

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0335409

DOI: 10.1371/journal.pone.0335409

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