Extracellular Vesicles as Biomarkers for Parkinson’s Disease: How Far from Clinical Translation?

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder affecting about 10 million people worldwide with a prevalence of about 2% in the over-80 population. The disease brings in also a huge annual economic burden, recently estimated by the Michael J Fox Foundation for Parkinson’s Research to be USD 52 billion in the United States alone. Currently, no effective cure exists, but available PD medical treatments are based on symptomatic prescriptions that include drugs, surgical approaches and rehabilitation treatment. Due to the complex biology of a PD brain, the design of clinical trials and the personalization of treatment strategies require the identification of accessible and measurable biomarkers to monitor the events induced by treatment and disease progression and to predict patients’ responsiveness. In the present review, we strive to briefly summarize current knowledge about PD biomarkers, focusing on the role of extracellular vesicles as active or involuntary carriers of disease-associated proteins, with particular attention to those research works that envision possible clinical applications.

Potential Exosome Biomarkers for Parkinson’s Disease Diagnosis: A Systematic Review and Meta-Analysis

“…(1) Participants included all PD patients diagnosed with PD regardless of factors such as stage, or presence of dementia. (2) The interventions reviewed in this study included evaluations of protein or miRNA PD biomarkers in exosomes in blood samples. (3) The comparator to PD patients was healthy controls.…”

“…Additionally, several studies have demonstrated elevated levels of α-syn in plasma neuronal-derived exosomes from PD patients compared to healthy controls [32,38,51,95]. It was reported that the interaction between α-syn and membranes plays a significant role in the conformational shifts of α-syn, potentially impacting protein functionality and contributing to aggregation in PD progression [2]. Furthermore, the aggregated and harmful variant of the protein, oligomeric α-syn, has been observed to engage with lipids, inducing structural alterations in lipid membranes.…”

“…Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease [1], affecting roughly 10 million people globally, with ~2% prevalence among those >80 years old [2]. PD is a disease in which parts of the brain are progressively damaged over several years, resulting in motor symptoms such as tremor, bradykinesia, rigidity, as well as physical and psychiatric symptoms such as depression, anxiety, anosmia, insomnia, memory problems, etc.…”

“…; (iii) inflammation-and immune system-related markers: TNF alpha, cytokine, etc. [2]; (iv) Alzheimer's disease-related markers: tau, presenilin, etc. [21]; (v) miRNA biomarkers: downregulation of miR-1, miR-22, and miR-29a, as well as the upregulation of miR-16-2, miR-26a-2, and miR-30a, in PD patients [22].…”