Repairing the Body Clock to Delay Alzheimer's Disease

Circadian sleep disruption is both a risk factor and a symptom of Alzheimer’s disease, and we will determine if restoring circadian rhythms in the brain can delay the disease.

Breakdown in circadian rhythm is both a risk factor and a symptom of Alzheimer’s. This suggests a vicious cycle of circadian disruption driving disease, and disease driving circadian disruption. If we could prevent circadian disruption, we may be able to prevent disease. The root cause of circadian dysfunction in Alzheimer’s is unclear. To address this, we will determine how tauopathy, a key component of Alzheimer’s disease, disrupts the function of the master circadian clock. We will also develop an approach to restore circadian rhythm in a disease model and determine if this prevents disease.

There is now a flourishing field of research targeting sleep in Alzheimer’s disease. However, the focus on sleep has left a hole in the field: What is the root cause of circadian disruption in Alzheimer’s? If we knew the root cause, we could devise approaches to fix it. This project focuses on answering this critical question by directly targeting the brain’s master circadian clock that controls circadian rhythms in our body.

This BrightFocus Award project will reveal how circadian rhythms break down in tauopathy and determine the therapeutic potential of restoring them.