Hyperexcitability and seizures in the THY-Tau22 mouse model of Tauopathy

Abstract. Epileptic seizures constitute a significant comorbidity of Alzheimer’s Disease (AD), which are recapitulated in transgenic mouse models of amyloidogenesis. Here, we sought to evaluate the potential role of Tau pathology regarding seizure occurrence. To this end, we performed intra-hippocampal electroencephalogram (EEG) recordings and PTZ (pentylenetertrazol) seizure threshold tests in THY-Tau22 transgenic mice of AD-like Tau pathology. We demonstrate that despite a lack spontaneous epileptiform activity in Tau22 mice, the animals display increased PTZ-induced seizure susceptibility and mortality. The increased propensity for induced seizures in THY-Tau22 mutants correlates with astrogliosis and increased expression of adenosine kinase, consistent with increased network excitability. These data support an impact of Tau pathology towards AD-associated seizures and suggest that Tau pathology may contribute to seizure generation in AD independent of Aβ pathology.