The crucial role of the sleep-wake system in Alzheimer’s Disease pathophysiology

We hypothesize that changes in the sleep/wake system, are crucial in the pathophysiology of AD. We propose that dysregulation of the LC is a key cause of hyperarousal in AD, and that it can be treated to improve AD symptoms and progression. To investigate this, we aim to study this system in detail in both mouse models for AD as in patients suffering from AD. In a second step, we will look at the effect of DORAs (and SORAs –selective orexin receptor antagonists-) on the sleep-wake system in the rTg4510 mouse model for tauopathy and in patients with AD and severe neuropsychiatric symptoms.