Tau activation of microglial cGAS–IFN reduces MEF2C-mediated cognitive resilience
Cornell University · MIND Research Institute · +7 more institutions
Abstract
Pathological hallmarks of Alzheimer's disease (AD) precede clinical symptoms by years, indicating a period of cognitive resilience before the onset of dementia. Here, we report that activation of cyclic GMP-AMP synthase (cGAS) diminishes cognitive resilience by decreasing the neuronal transcriptional network of myocyte enhancer factor 2c (MEF2C) through type I interferon (IFN-I) signaling. Pathogenic tau activates cGAS and IFN-I responses in microglia, in part mediated by cytosolic leakage of mitochondrial DNA. Genetic ablation of Cgas in mice with tauopathy diminished the microglial IFN-I response, preserved synapse integrity and plasticity and protected against cognitive impairment without affecting the…
Citation impact
- FWCI
- 32.36
- Percentile
- 100%
- References
- 73
Authors
29- JCJoe C. UdeochuCorresponding
Cornell University, MIND Research Institute, Weill Cornell Medicine
- SASadaf Amin
Cornell University, MIND Research Institute, Weill Cornell Medicine
- YHYige Huang
Cornell University, MIND Research Institute, Weill Cornell Medicine
- LFLi Fan
Cornell University, MIND Research Institute, Weill Cornell Medicine
- EREileen Ruth S. Torres
Cornell University, MIND Research Institute, Weill Cornell Medicine
Topics & keywords
- Tauopathy
- Neuroscience
- MEF2C
- Microglia
- Biology
- Neuroinflammation
- Cognitive decline
- Mef2