2024 Alzheimer's Association Research Fellowship (AARF)

Dissecting the Role of Astrocyte Network in AD-Associated Sleep Disturbance

How may changes in calcium levels in the brain impact sleep disturbances associated with Alzheimer’s? 

Baoling Lai, Ph.D.
New York University Grossman School of Medicine
New York, NY - United States

Background

Recent studies reveal that sleep disruption or poor sleep patterns may impact the risk of developing Alzheimer’s and other brain diseases and may precede cognitive impairment for several years. Short sleep duration and poor sleep quality have been linked with Alzheimer’s-related brain changes, including the build-up of beta-amyloid and tau in the brain. Studies have also linked poor sleep quality and sleep duration that is either too long or too short with poorer cognitive performance.
  
Past studies suggest a way that sleep loss may disturb brain function is through a reduction of the ability of brain cells to communicate with each other. Calcium is essential for the function of all cells and is particularly important for communication between nerve cells in the brain. Calcium levels inside brain cells must be regulated closely, since abnormal calcium levels may cause cell damage or death. In Alzheimer’s, the accumulation of beta-amyloid and tau impacts helper cells in the brain called astrocytes, disrupting calcium activity and cell-to-cell communication. However, exactly how astrocyte dysfunction contributes to Alzheimer’s-associated sleep disturbances remains unclear.

Research Plan

Dr. Baoling Lai and colleagues believe that changes in calcium activity within astrocyte networks in the brain may lead to increased sleep disturbances in individuals with Alzheimer’s and contribute to Alzheimer’s-associated brain changes. The researchers will use a state-of-the-art brain scan technique called in vivo two-photon calcium imaging to measure the calcium activity associated with astrocytes inside living Alzheimer’s-like mice. They will also measure sleep/wake activity with electroencephalography (EEG), which measures electrical signals in the brain, and electromyography (EMG), which measures muscle activity. Dr. Lai and colleagues will evaluate how changes in astrocytic calcium levels may impact sleep disturbance in mice with early Alzheimer’s-like brain changes. They will then study the biological mechanisms through which astrocytic calcium levels impact sleep disturbances in the mice.

Impact

The results of this project may provide a better understanding of how sleep alterations may promote dementia risk in older individuals. If successful, the findings may support new potential targets for developing therapies aimed at alleviating sleep disorders and cognitive decline associated with Alzheimer’s.