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2022 Alzheimer's Association Research Grant (AARG)

Circadian Regulation of the Choroid Plexus in Brain Aging.

Can age-related changes in a specific brain region impact sleep quality and possibly lead to dementia?

Aleksandra Deczkowska, Ph.D.
Institut Pasteur
Paris, France



Background

Circadian rhythms are natural biological changes that occur over an approximately twenty-four hour cycle, which is often called the sleep-wake cycle. These rhythms usually respond to the amount of light and darkness in an environment, and they involve daily patterns of sleeping, eating and other activities. Disruptions to circadian rhythms can alter people’s ability to get proper sleep. More than 50% of individuals with dementia experience sleep disruptions or poor sleep patterns that precede cognitive (brain function) impairment by several years. Past studies suggest that sleep loss may reduce brain function by impairing the ability of brain cells to communicate with each other or by damaging certain brain structures. 

Initial studies by Dr. Aleksandra Deczkowska and colleagues found that genes involved in maintaining circadian rhythms become abnormally regulated in a brain region called the choroid plexus. This region produces cerebrospinal fluid (or CSF, a type of biological fluid found in the brain and spinal cord). These findings suggest that age-related changes in the choroid plexus may lead to circadian rhythm dysfunction in dementia.

Research Plan

Building upon their initial research, Dr. Deczkowska and team will conduct a deeper  study of circadian rhythms and the aging choroid plexus. They will examine how turning on and off circadian rhythm genes in the choroid plexus differs in young and old mice. They will then expose the young mice to changes in normal light conditions (mimicking the way people with jet-lag may experience these changes), as well as other changes known to alter sleep. They will test whether these changes impact how the choroid plexus regulates circadian rhythm function. Next, using middle-aged mice, the researchers will delete a choroid plexus gene related to circadian rhythms to assess whether the loss of this gene impacts memory and other cognitive functions in the animals, and whether it leads to brain inflammation and other dementia-related brain changes. Dr. Deczkowska’s team will then look for ways that cells in the choroid plexus communicate with cells in other regions of the brain to maintain circadian rhythms.

Impact

Results from this study could shed new light on how improper sleep impacts brain health and could lead to new sleep-related approaches for reducing the risk of dementia.

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