BME PhD Preliminary Exam Announcement for Brendan K. Ball (D. Brubaker, advisor)

Everyone is invited to attend the public presentation beginning at 11:00AM.

Title: Alzheimer’s Disease Pathology Driven by Orexin and Type 2 Diabetes

Date & Time: Monday, May 8th @ 11:00AM

Location: Hybrid via MJIS 2001 and Zoom (https://purdue-edu.zoom.us/j/5554725555) 

Committee Members: Doug Brubaker, Ph.D. (Chair), Elizabeth Proctor, Ph.D., Deva Chan, Ph.D., Tamara Kinzer-Ursem, Ph.D., Brendan Lucey, M.D.

Abstract: Alzheimer’s disease (AD) is the most common form of dementia and is often presented with aggregates of amyloid-β and intracellular tau proteins in the brain, which leads to downstream progressive memory loss and cognitive impairment. Multiple risk factors for AD development include age, genetics, and other pre-existing diseases such as type 2 diabetes (T2D). While up to 81% of people with AD may have T2D or impaired glucose levels, the biological mechanisms by which T2D exacerbates AD pathology are not well-understood. Previous studies shown that orexin, a neuropeptide responsible for appetite, arousal, and wakefulness, to be involved in AD and T2D pathology, which may be a potential link between the two diseases. We propose that protein aggregation in the brain, and metabolic processes regulated by the orexin network and T2D exacerbates AD pathology. To test this idea, we will first identify functional and biological associations of gene expressions via protein interaction networks and gene set enrichment analysis. Second, we will incorporate publicly available mouse, post-mortem human brain tissue, and human cell line transcriptomic data into our computational model to characterize pathways by which proteinopathy, T2D and orexin are predictive of human neuropathological status. Finally, we will quantify neuroinflammatory cytokines and gene expression by performing multiplexing assays and RNA sequencing of primary neuron samples after stimulation with disease-associated metabolites and orexin antagonist. Upon completion of this study, we will have improved our understanding on biological mechanisms in which orexin and T2D exacerbates AD pathology, which may introduce avenues for disease-directed therapeutics.