# Oxidative Stress—Related Serum Extracellular Vesicle miRNAs Indicate Symptom Severity and Cognitive Decline in Parkinson's Disease

## TL;DR

This study identifies specific microRNAs in blood serum extracellular vesicles that are linked to symptom severity and cognitive decline in Parkinson's disease patients.

## Contribution

The study introduces oxidative stress-related serum extracellular vesicle miRNAs as potential biomarkers for Parkinson's disease progression.

## Key findings

- Upregulation of miR-126-5p is strongly associated with cognitive decline in Parkinson's disease.
- Downregulation of miR-24-3p correlates with increased motor symptom severity.
- Reduced levels of miR-320a-3p are linked to impaired quality of life in PD patients.

## Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non‐motor symptoms, including cognitive decline and reduced quality of life. Identifying reliable biomarkers for disease progression and symptom severity remains a critical challenge. In this study, levels of oxidative stress–related microRNAs (miR‐24‐3p, miR‐103a‐3p, miR‐320a‐3p, miR‐494‐3p, miR‐126‐5p, and miR‐543) within blood serum extracellular vesicles (EVs) were examined in a cohort of 93 PD patients to assess their associations with cognitive function, symptom severity, quality of life, and other clinical characteristics. The methods included microRNA extraction from blood serum EVs, followed by cDNA synthesis and RT‐qPCR for expression analysis. Upregulation of miR‐126‐5p, as well as downregulation of miR‐24‐3p showed the strongest associations with symptom severity and cognitive decline, whereas downregulated miR‐320a‐3p levels correlated with patient‐reported quality of life in PD patients. Downregulation of miR‐103a‐3p, and miR‐543 expression showed slight associations with motor symptoms, cognitive function, and quality of life domains; however, some of these associations lacked statistical power. These findings indicate that specific microRNA expression profiles in extracellular vesicles are associated with PD symptom severity and progression, supporting their further evaluation as biomarkers in larger independent cohorts.

Oxidative stress and mitochondrial dysfunction are core mechanisms to dopaminergic neuronal death in Parkinson's disease (PD) and are regulated by microRNAs such as miR‐24‐3p, miR‐103a‐3p, miR‐320a‐3p, miR‐494‐3p, miR‐126‐5p, and miR‐543. Their expression was analyzed in serum extracellular vesicles of 93 PD patients by RT‐qPCR, as well as correlations with cognition, motor symptoms, and quality of life. MiR‐126‐5p overexpression was linked with cognitive decline. Downregulation of miR‐24‐3p was correlated with motor severity, and reduced levels of miR‐320a‐3p were associated with impairment in quality of life. These findings confirm the potential of extracellular vesicle‐derived microRNAs as biomarkers for PD progression.