BME PhD Preliminary Exam Announcement for Jee Hyun Park (D. Brubaker, advisor) Everyone is invited to attend the public presentation beginning at 10:00 AM. Research Title: Characterizing the Roles of Sleep and Apolipoprotein E Epsilon 4 Allele in Alzheimer's Disease Date, Time and Location: April 18th, 2024, at 10:00 AM, MJIS 2001 Thesis Committee Members: Douglas Brubaker, Ph.D. (Chair) Deva Chan, Ph.D. Yunjie Tong, Ph.D. Tzu-Wen Cross, Ph.D. Abstract: Alzheimer's Disease (AD) is a neurodegenerative disease that impedes cognitive function. The primary features of AD are amyloid beta and tau depositions. Another distinctive characteristic of AD is lipid droplets in glial cells. For late-onset AD, apolipoprotein (APOE) e4 prompts elevated risk. Similarly, sleep loss is another risk factor that impacts the progression of the disease. However, the potential relationship between APOE4 and sleep deprivation is not fully understood. Researchers have demonstrated that higher expression of orexin leads to elevated wakefulness. Parallel to increased orexin levels, amyloid beta levels have been shown to rise. Also, APOE4 promotes AD hallmark accumulation and lipid droplet formation in glial cells, leading to detrimental inflammation. Thus, we hypothesize that APOE4 and sleep loss further inflict damage to progress AD through metabolic dysfunction of glial cells. To explore our hypothesis, we will examine transcriptomic data of each glial cell type of AD APOE4 and APOE3 carrying humans and discover metabolic pathways disrupted and characteristic of disease shared with the orexin network. In addition, we will investigate metabolomics and transcriptomics of aged APOE4 and APOE3 mice brain samples for dysregulated metabolite and gene expression levels. We will pair transcriptomics data of mice with the different APOE isoforms with transcriptomics of sleep-deprived mice to observe aligned pathways that could be targets for an orexin inhibitor. Our study will determine metabolic impairment as a connection between sleep deprivation and APOE4 and explore orexin antagonists as a potential treatment for reducing AD progression.