Tau pathology induced alteration in neuronal activity disrupt sleep and cerebral metabolic rhythms in the P301S PS19 mouse model of tauopathy

Blood glucose levels in P301S mice fail to rise in response to glucose injection. Brain glucose/lactate fluctuations are maintained suggesting tau pathology preserves glucose utilization. Conversely, decreased NREM and REM and increased wake were exhibited with tau pathology. EEG spectral analysis indicates decreased beta activity, suggesting diminished GABA activity. Increased theta during NREM suggests increased pressure to transition to REM sleep. Reduced sleep drive is illustrated by increased delta in wake. Together, tau pathology reduces sleep drive and ability to switch between vigilant states despite increased sleep need. These results suggest that tau pathology causes excitatory/inhibitory imbalance and sleep impairment but does not contribute to profound effects on cerebral metabolic rhythms.