Author Date

2026-02-13

Degree Name

BS

Department

Chemistry and Biochemistry

College

Life Sciences

Defense Date

2026-02-19

Publication Date

2026-03-09

First Faculty Advisor

John Calvin Price

First Faculty Reader

David Hansen

Honors Coordinator

Brandon Gassaway

Keywords

Proteomics, ApoE, Alzheimers, Metabolism, Mouse, Mitochondria

Abstract

Apolipoprotein E (ApoE) is an important lipid transporter in the brain. There are three different ApoE variants: ApoE2, ApoE3, and ApoE4. Each of these variants either contribute to or protect against Alzheimer’s disease (AD). The Hippocampus (HC) and the Entorhinal Region (ER) of the brain consistently develop AD pathology first. We hypothesize that ApoE variants affect lipid and protein metabolism in these regions more strongly than in others. Differences in the regional regulation and the ApoE-isoform impacts of these metabolic pathways remain unknown.

We measured brain protein turnover rates in ApoE knock-in mice labeled with deuterated water. Using a laser capture microscopy and Liquid-Chromatography Mass-Spectrometry (LC-MS), we quantified the differences in turnover rate and concentration for thousands of proteins in multiple brain regions. For the regional analysis, we collect 200x200x20 micrometer samples from the HC, ER, and Visual Cortex (VC), and compare them to the Cerebellum (CB) as a control since it experiences less neurodegeneration. I present a replicable method capable of specifically and accurately addressing each microsample taken from the mouse brain areas. To accomplish this we created a software that receives an input of an experimental mouse brain sagittal tissue section and accurately reports the depth that the sample was collected from. This provides information on where in the brain we are sampling, allowing us to find patterns in proteomics corresponding to specific areas of the brain.

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