Author ORCID Identifier

https://orcid.org/0000-0002-0090-1584

Date Available

5-11-2024

Year of Publication

2024

Degree Name

Master of Science (MS)

Document Type

Master's Thesis

College

Pharmacy

Department/School/Program

Pharmaceutical Sciences

First Advisor

Dr. Anika Hartz

Abstract

Introduction: Alzheimer’s disease (AD) is a neurodegenerative disease with neuropathological changes in the blood-brain barrier that offers possible therapeutic targets. Oxidative stress is one driving factor for AD. NADPH oxidase 2 (NOX2) in the capillary endothelium produces reactive oxygen species, leading to oxidative stress-mediated blood-brain barrier dysfunction. We hypothesized that using a specific NOX2 inhibitor, PhoxI2, has the potential to reduce reactive oxygen species and repair amyloid-β (Aβ)-driven blood-brain barrier leakage in an AD mouse model.

Methods: For this study, 5xFAD (Familiar Alzheimer Disease) mice were treated with vehicle or PhoxI2, a NOX2 inhibitor. Techniques utilized were Enzyme-Linked Immunosorbent Assay (ELISA) to measure plasma S100b, a biomarker for blood-brain barrier leakage, and ELISAs for Aβ40 and Aβ42 of both plasma and brain samples to gauge if there is any benefit for Aβ levels. Bradford assay was used to normalize protein concentrations for ELISAs.

Results: Our results demonstrate significantly lower S100β plasma levels in the treatment group compared to the 5xFAD cohort, approaching levels seen in WT mice (males: p < 0.0001; females: p < 0.0001). These findings support the hypothesis that NOX2 contributes to blood-brain degradation in AD and could be a target for future therapeutics.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2024.154

Funding Information

2R01AG039621; Hartz (PI) 01/01/2018 – 08/31/2023

Title: Restoring Blood-Brain Barrier Function to Improve Cognition in Alzheimer’s Disease

Sponsor: National Institutes of Health/National Institute on Aging

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