Locus coeruleus - Sleep Gatekeeper Malfunction in AD and PD
How does the malfunction of a small brainstem region that controls sleep contribute to early brain damage in Alzheimer’s and Parkinson’s disease?
Background
Sleep problems are among the earliest symptoms of Alzheimer’s and Parkinson’s disease, often appearing years before memory loss or movement problems. A small brain region in the brainstem called the locus coeruleus plays a key role in controlling sleep, alertness, and stress responses. This region uses the chemical messenger norepinephrine to help regulate when the brain is awake or asleep. Importantly, the locus coeruleus is one of the first brain regions damaged in both Alzheimer’s and Parkinson’s disease. Scientists believe that abnormal activity in this region may disrupt sleep and, over time, contribute to brain degeneration. However, it remains unclear whether sleep disruption is simply an early warning sign of disease or whether disturbed sleep actively damages the locus coeruleus and accelerates brain degeneration.
Research Plan
Anita Luthi, Ph.D., from University of Lausanne and Matthias Prigge, Ph.D., from Humboldt University will collaborate to study how changes in locus coeruleus activity affect sleep and brain health. Using mouse models that mimic early features of Alzheimer’s and Parkinson’s disease the researchers will monitor sleep patterns, brain activity, body temperature, and chemical signaling in the brain over time using advanced recording techniques. They will then directly increase or decrease activity in the locus coeruleus to test whether abnormal activity alone can cause sleep problems and brain damage. Finally, the researchers will specifically limit rapid eye movement (REM) sleep, a sleep stage that normally silences this brain region, to determine whether REM sleep plays a protective role in maintaining brain health.
Impact
This study could reveal how early sleep disruption contributes to brain degeneration in Alzheimer’s and Parkinson’s disease. By identifying sleep stages and brain circuits that protect brain cells in the locus coeruleus, this study will knowledge to point to new strategies that use sleep regulation to slow or prevent neurodegeneration before severe symptoms appear.