2023
Myelin, the protective insulation surrounding nerves that enables efficient neural transmission in the brain, is vital for brain function and dysregulated in Alzheimer’s disease (AD). However, the role of myelin and oligodendroglia, the cells that produce myelin, in the onset and progression of AD remains incompletely understood. Sleep and circadian deficits are also commonly identified in patients with AD, with many of these disturbances proceeding the onset of typical AD symptomology. How sleep and the circadian system may intersect with myelin and oligodendroglial biology in AD remains unclear. To enhance the efficacy of therapeutic strategies for AD, it is imperative to better understand the molecular mechanisms governing the function of the circadian clock and myelination in AD. The Gibson lab recently identified that the circadian molecular machinery strongly regulates myelin and oligodendroglial dynamics, which change throughout aging. Using mouse and human-induced pluripotent stem cell models, this application will investigate the role of circadian rhythm in oligodendroglia and myelination and how these rhythms affect sleep patterns in the context of AD. The overall goal of this work is to better understand why sleep disturbances are commonly identified in AD. By understanding how these disruptions affect oligodendroglial dynamics and myelination in AD, we aim to provide insights into the progression of AD and have a positive impact on the development of novel therapeutic treatments.