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

## TL;DR

Blocking interleukin-1 receptor signaling did not reduce mature tau pathology in two mouse models, suggesting it may not be an effective treatment for tau-related diseases.

## Contribution

The study shows that IL-1RA gene therapy is ineffective in reducing tau pathology in pure tauopathy models.

## Key findings

- IL-1RA over-expression did not significantly improve tau pathology in rTg4510 or PS19 mouse models.
- Il1b gene expression was significantly increased, but IL-1β protein levels were only slightly elevated.
- The results suggest IL-1RA may not be a viable treatment for pure tauopathies.

## 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.