Recent developments in the quest for a blood biomarker to diagnose and monitor Parkinson’s disease have brought researchers one step closer to personalizing treatment and improving the lives of those affected. In a breakthrough study, scientists from the WEHI Parkinson’s Disease Research Center have identified changes in the abundance of blood immune cells as a potential indicator of Parkinson’s disease progression. This discovery is particularly significant in a disease where there has yet to be a reliable, non-invasive diagnostic test. The study, part of the world’s largest investigation of its kind, analyzed data from over 500,000 participants, making it a pivotal contribution to Parkinson’s research.
Parkinson’s disease is a neurodegenerative disorder that progressively impairs movement and function. It is the second most common neurodegenerative condition after Alzheimer’s disease, and its prevalence is rising rapidly. Parkinson’s has no known cure, and current treatments mainly focus on alleviating symptoms, rather than slowing or halting the disease’s inevitable progression. Around 200,000 Australians live with Parkinson’s, and almost 40 individuals are diagnosed every day. In the next 15 years, these numbers are expected to double. Without an accurate clinical diagnostic test, the exact number of people suffering from Parkinson’s remains uncertain.
The research team from the Parkinson’s Disease Research Center, spearheaded by Professor Melanie Bahlo and Dr. Fei Wang, worked collaboratively with various groups within WEHI, including the Human-based Research and Clinical Trials group, Research Computing, and the Bahlo and Dewson labs. Their findings shed new light on the intricate relationship between blood immune cells and Parkinson’s disease. This research brings hope that, in the near future, blood tests might serve as reliable tools for diagnosing and tracking the disease, improving clinical outcomes for patients.
Professor Bahlo emphasized the long-term goal of developing a screening test for Parkinson’s that is as simple and accessible as current programs for diseases like bowel cancer. Early diagnosis through such a screening method would enable patients to access treatment faster, potentially slowing the disease’s progression before it causes irreversible damage.
For decades, mitochondrial dysfunction has been closely linked to Parkinson’s disease. Mitochondria, the cellular powerhouses that produce energy, contain their own genetic material—distinct from nuclear DNA. It has been hypothesized that an imbalance in the number of mitochondrial DNA copies, known as mtDNA-CN, could serve as a marker for the disease. The reasoning was that mitochondrial dysfunction leads to the decline of cellular function, particularly in neurons, which is characteristic of Parkinson’s. However, the new study reveals that this connection may not be as straightforward as previously thought.
Using a novel method, the WEHI team developed a software algorithm to estimate the mtDNA-CN in blood samples, enabling them to study a larger, more diverse dataset than ever before. Initially, they tested the algorithm on a sample of over 10,000 participants, expecting to observe a clear correlation between lower mitochondrial DNA levels and an increased risk or severity of Parkinson’s disease. But the results were unexpected. Lower mitochondrial DNA counts in the blood were not directly related to Parkinson’s, and this perceived connection disappeared when the researchers considered the blood cell types present. This led them to question whether mitochondrial dysfunction alone could explain the disease’s onset and progression.
Upon further analysis, they found a more significant link between Parkinson’s and certain immune cells in the blood, especially neutrophils and lymphocytes, two types of white blood cells crucial to immune function. It is well-documented that neuroinflammation is a characteristic feature of Parkinson’s, so this finding suggests that the immune response, rather than mitochondrial dysfunction, could be more directly related to the disease’s progression. The study’s results mark a critical shift in understanding the potential biomarkers for Parkinson’s and offer new avenues for diagnosis and treatment.
Expanding the study’s reach, the research team replicated their findings using the extensive UK Biobank dataset, which contains data from nearly 500,000 participants. This secondary analysis confirmed their initial results, reinforcing the robustness and applicability of their methodological framework. By utilizing the WEHI-developed mitoCN software, the study was able to provide accurate, efficient estimates of mitochondrial DNA copy numbers, which the research community can now leverage. To foster future studies beyond Parkinson’s disease, the team has made the mitoCN software publicly available for use worldwide.
This new development also brings researchers closer to the promise of a simple blood test for Parkinson’s. In 2023, the Michael J. Fox Foundation identified a promising new biomarker based on spinal fluid to detect the presence of alpha-synuclein, a protein that forms toxic aggregates in Parkinson’s disease. However, because this test requires an invasive spinal tap, it presents limitations in accessibility and practicality. In contrast, a blood test is non-invasive, relatively inexpensive, and much easier to use on a larger scale, making it an ideal alternative for clinicians. Dr. Fei Wang highlighted the potential of blood biomarkers to track disease progression, assess treatment efficacy, and even measure the impact of new therapies in clinical trials.
The ultimate goal of identifying such biomarkers goes beyond diagnosis; they will also have significant clinical implications for patient care. Biomarkers could allow doctors to monitor the progression of Parkinson’s disease, adjusting treatments to ensure the highest quality of life for patients. This could include optimizing medications to manage symptoms more effectively or predicting the disease’s course and planning interventions at the right time.
With this groundbreaking research, scientists are one step closer to not just understanding Parkinson’s disease better, but also offering more personalized, accessible treatment options for those affected. These advancements offer renewed hope for the future of Parkinson’s care, with the prospect of developing a blood test capable of both diagnosing and tracking the disease. Moving forward, these findings promise to drive further innovations, contributing to a world where earlier, more effective treatments can slow the progression of Parkinson’s disease and ultimately improve outcomes for millions of people worldwide.
Reference: Longfei Wang et al, Peripheral immune cell abundance differences link blood mitochondrial DNA copy number and Parkinson’s disease, npj Parkinson’s Disease (2024). DOI: 10.1038/s41531-024-00831-x