Does Pathology in Locus Coeruleus Trigger AD?

The locus coeruleus (LC) of the brain is important for sleep and memory, but it’s unclear if accumulation of tau in its neurons is an early sign of Alzheimer’s disease. By studying the electrical activity of LC neurons in mice, we will determine if tau prevents LC to function normally and causes sleep and memory problems. In addition, we will manipulate the activity of the LC neurons in order to restore its function and reverse sleep and memory impairment.

Tau, one of the hallmark pathologies of AD, accumulates in the locus coeruleus of 20-year-old healthy adults, and yet, its consequences remain unknown. To mimic tau accumulation in the LC, we will extract tau from human AD brains and inject it into the LC of mice. We will then monitor sleep and test memory determine if tau impacts sleep prior to the onset of AD-like cognitive symptoms. A major innovation of this project is to be able to predict the onset of AD. The study pioneers the use of multi-region electrodes to probe brain regions involved in sleep and memory combined with machine learning approach to predict early symptoms of AD. Additionally, the project aims to reverse LC dysfunction using optogenetic tools.

The results of this study will inform and help predict if sleep disturbances in young adults are important predictors Alzheimer’s disease.