Degree Name

Department

Chemistry and Biochemistry

College

Computational, Mathematical and Physical Sciences

Defense Date

2026-02-19

Publication Date

2026-03-25

First Faculty Advisor

JC Price

First Faculty Reader

David Hansen

Honors Coordinator

Brandon Gassaway

Keywords

alzheimer's disease, lipidomics, biochemistry, mass spectrometry, neurodegeneration, APOE

Abstract

Apolipoprotein E gene (APOE) and its associated isoforms are the most significant genetic risk factors for Alzheimer’s disease (AD). The common alleles, APOE2/3/4, exhibit a protective/neutral/risk-inducing impact on sporadic AD development respectively. Our lab’s research focuses on APOE modification of the brain proteome and lipidome, with an emphasis on regional regulation and interest in assessing how APOE4 affects regulation differently between distinct regions of the brain. This thesis presents an analysis of cryosectioned brain samples harvested from young APOE knock-in mice. Using metabolic labeling with deuterated water, we measure turnover and dietary sourcing of lipids. We observe significant differences in lipid metabolic regulation between APOE3 and 4. Using kinetic analysis, we identify mechanistic regulatory actions specific to brain regions, providing nuance to our abundance findings and elucidating why we are seeing these changes. This analysis provides greater insight into how APOE isoforms affect lipid metabolism in various regions of the brain, allowing hypothesis testing and opening up the door to new possibilities in clinical diagnosis and treatment.