Date of Award

Spring 6-13-2026

Document Type

Undergraduate Honors Thesis

Degree Name

B.S. in Biological Sciences, Psychology

Organizational Unit

College of Natural Science and Mathematics, Biological Sciences

First Advisor

Daniel A. Linseman

Second Advisor

Casey C. H. Barker

Third Advisor

Schuyler van Engelenburg

Fourth Advisor

Yan Qin

Copyright Statement / License for Reuse

All Rights Reserved
All Rights Reserved.

Keywords

Alzheimer's disease, Neuroinflammation, Exosomes, Extracellular vesicles, Astrocytes, Microglia

Abstract

Alzheimer’s disease (AD) is the leading cause of dementia, for which the biggest risk factor is aging. AD pathology consists of amyloid plaques and neurofibrillary tangles, accompanied by neuroinflammation. Previous research has investigated inflammation via cytokine biomarkers in brain tissue, blood samples, and exosomes derived from plasma; however, more research is needed to accomplish the goal of creating a prognostic blood test for AD. Exosomes are small, extra-cellular vesicles released from cells that contain various forms of cargo. Astrocytes and microglia are two types of glia cells, both of which become activated in AD and contribute to neuroinflammation. This study introduces and validates a novel protocol for isolating astrocyte-derived and microglia-derived exosomes from mouse brain tissue using an immunoaffinity magnetic bead-based technique. Validation methods included transmission electron microscopy(TEM), nanoparticle tracking analysis (NTA), and western blotting. This protocol was used to isolate exosomes from four different mouse groups: old 3xTg-AD, young 3xTg-AD, old wild-type, and young wild-type. The exosome cargo was analyzed using a GFAP ELISA and a ProcartaPlex cytokine panel to assess inflammatory markers. IL-6, G-CSF, and IL-33 concentrations were found to be significantly higher in the old 3xTg-AD mice than the aged wild-type and disease matched mouse groups. Microglia-derived exosomes had minimal differences in cytokine concentrations across groups. The validation of this protocol allows for further analysis of cell type specific exosomes in the 3xTg-AD and other mouse models. Analysis of astrocyte-derived exosomes indicate higher levels of neuroinflammation in old 3xTg-AD mice, and these findings indicate thatIL-6, G-CSF, and IL-33 have the potential to be used as exosome biomarkers in AD.

Copyright Date

5-21-2026

Publication Statement

Copyright is held by the author. This work may only be accessed by members of the University of Denver community. The work is provided by permission of the author for individual research purposes only and may not be further copied or distributed. User is responsible for all copyright compliance.

Rights Holder

Sabrina C. Efroymson

Provenance

Received from Author

File Format

application/pdf

Language

English (eng)

Extent

31 pgs

File Size

880 KB

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