Thesis Format
Monograph
Degree
Master of Science
Program
Anatomy and Cell Biology
Supervisor
Whitehead, Shawn
2nd Supervisor
Pasternak, Stephen
Co-Supervisor
Abstract
Parkinson’s Disease (PD) is a common neurodegenerative disease that is projected to increase in prevalence with the aging population. Current diagnosis of PD is based on clinical criteria as there exists no objective biomarker capable of diagnosing the disease. Clinical trials into protein biomarkers of PD have concentrated on analyzing cerebrospinal fluid (CSF). Although CSF is ideal due to its intimate relationship with cells of the central nervous system, obtaining it is relatively invasive. In contrast, brain-derived extracellular vesicles (EVs) are found to be in substantial concentrations in systemic circulation, allowing for the possibility of a diagnostic blood test. In this study, we demonstrate that a higher concentration of alpha synuclein (aSyn) and phosphorylated tau181 (p-tau181) EVs are present in PD plasma when compared to plasma from HCs. Further research is needed to determine if correlation exists between EV concentration and clinically determined values.
Summary for Lay Audience
Parkinson’s disease (PD) is a progressive disease of the brain that mainly effects a group of cells called dopaminergic neurons. These cells are involved in movement initiation and modulation. In a healthy brain, dopaminergic neurons work in concert with other cells of the brain to ensure smooth movement of voluntary actions. However, in the brain of someone with PD, much of the dopaminergic cell population is depleted, leading to slowness of movement, shaking, and disrupted posture. Research into PD has found proteins that are associated with the disease and one of the most emphasized is called alpha synuclein (aSyn). This protein is widely believed to be related the cell death seen in PD, and as such, scientists are interested in using it as an indicator (biomarker) of the disease. Using a procedure that removes the fluid that bathes the cells of the brain, scientists can check for aSyn levels and compare the levels found in PD brains to those found in healthy brains. However, this procedure is quite invasive and the protein floating around in the fluid is subject to degradation over time, which is why in the more recent years biomarker research has expanded to include extracellular vesicles (EVs). EVs are tiny packages that are released by cells into the space that surrounds them. These EVs contain many proteins (e.g., aSyn) and other molecules and since they are protected by an outer layer, it helps to prevent them from degradation. A great benefit of EVs is that they can cross the barrier that separates the brain from the rest of the body, allowing us to collect them from blood! In this study, we used an instrument — called a nanoflow cytometer — that is able to detect these tiny EVs in blood so that we could compare determine if the aSyn levels differ between healthy individuals and in those with PD.
Recommended Citation
Flondra, Kaitlyn M., "Brain-derived Extracellular vesicles as biomarkers of Parkinson’s disease" (2023). Electronic Thesis and Dissertation Repository. 9503.
https://ir.lib.uwo.ca/etd/9503