Closed-loop orexin receptor modulation to entrain circadian glymphatic clearance in neurodegeneration via orexin-AQP4 astrocyte coupling

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Drawing from Alzheimer's disease evidence that neuromodulation restores circuit-level oscillations, we propose that targeted orexin receptor agonism (OX1R/OX2R) can entrain circadian glymphatic clearance by coupling orexinergic arousal signaling to astroglial AQP4 polarization along perivascular pathways. This approach would use a closed-loop system—tracking sleep-wake EEG signatures and deliverin