Background
The existence and contribution of microglia with senescent-like alterations in the pathogenesis of age-related neurodegenerative diseases like Alzheimer's disease (AD) have been suggested in recent years. However, the identification of this distinct microglial population in vivo has proven challenging, largely due to overlaps in the inflammatory phenotype of activated and senescent microglia. Furthermore, attempts at recapitulating senescence in microglia in vitro are limited.
Conclusion
Our characterization of senescent microglia can be used to better understand the role of senescent microglia in various age-related contexts, including whether clearance of senescent microglia represents a viable therapeutic option.
Methods
We analyzed the RNA expression patterns of individual microglia from normal mice and the pathogenic tau P301 S PS19 mouse model. We have previously demonstrated that p16-expressing senescent microglia occur in these mice when neurodegeneration has occurred.
Objective
To identify and characterize senescent microglia that occur in vivo in an animal model of neurodegeneration driven by pathologic tau.
Results
Here we identify a subset of disease-associated microglia with senescent features, notably characterized by the expression of Ccl4. This signature overlaps with established markers of senescence from other cell types.