People with Alzheimer’s disease (AD) often struggle with sleep—feeling very sleepy during the day, unable to sleep well at night, and losing the regular daily rhythm that tells our bodies when to sleep and wake. These problems appear early, worsen quality of life, and may speed up the disease. This project asks a simple question with powerful implications: which tiny brain areas that normally control deep sleep, dream sleep (REM), and the body’s 24-hour clock are damaged in different forms of AD—and what molecular changes accompany that damage?
By contrasting different AD variants that selectively affect these sleep-control nuclei, we can treat the disease itself as a kind of “natural experiment.” Because we cannot ethically manipulate human sleep circuits—and because human sleep differs from animal models—this approach lets us infer what each nucleus contributes to specific aspects of sleep and circadian timing. These insights should enable more precise, personalized treatments that target the right circuit for the right patient. If we are successful, AD-variant–specific sleep signatures could support clinical care—for example, guiding therapy in stages when amyloid and tau biomarkers are already present but before life-denying symptoms emerge—and continuous sleep monitoring could provide a practical way to track whether a treatment is working.
