Targeting Sleep Deficits to Restore Memory Function in Alzheimer's Disease

We aim to improve memory function in Alzheimer’s disease by improving sleep quality. This will be achieved by activating a specific group of neurons whose activity is impaired in Alzheimer’s disease. A particular period during sleep that is termed slow-wave sleep is associated with memory performance and is also disrupted in Alzheimer’s disease. Scientific evidence suggests that a specific group of neurons are responsible for slow-wave sleep regulation. This project aims to improve the function of these neurons through two different approaches. The first approach will utilize a novel technology to activate these neurons, followed by assessing memory in Alzheimer’s disease animal models. The second approach will rely on pharmacological approaches to support the function of these neurons.

Although numerous efforts have been attempting to find a cure for Alzheimer’s disease by targeting the traditional disease hallmarks, no treatment is currently available. Therefore, new approaches to target disease pathology are urgently needed. Sleep is disrupted early in the course of the disease. A particular period during sleep that is termed slow-wave sleep is closely associated with memory performance in healthy individuals and is also disrupted in Alzheimer’s disease. Scientific evidence suggests that a particular group of neurons are responsible for slow-wave sleep regulation. This project aims to find and activate this group of neurons and improve their function in Alzheimer’s disease mouse models through two different approaches. The first approach will utilize a novel genetic technology to activate these neurons with light, followed by assessing memory and pathology of Alzheimer’s disease in animals. This method will provide an essential proof of concept for the role of these neurons in Alzheimer’s disease-related sleep deficits. The second approach will rely on pharmacological approaches to support the function of these neurons. If successful, this method will be easier to translate to the clinic. The outcome of these experiments will allow us to understand the role of sleep in Alzheimer’s disease and offer a new therapeutic target for Alzheimer’s disease.

We use state-of-the-art technology such as optogenetics which allows us to control neuronal activity using light. In addition, we also use multiphoton microscopy to image the brain in action in living animals.

Our study has two foreseeable benefits to the public. First, it will increase our understanding of the role of sleep in Alzheimer’s disease and, therefore, will lead and direct future research efforts in the field. Second, our experiments can potentially lead to a discovery of a successful therapeutic for Alzheimer’s disease.