Parkinson’s is the fastest growing neurological disorder worldwide and second in prevalence to Alzheimer’s. Parkinson’s is neurodegenerative, meaning it will continue to get worse over time, and there is still no cure or drugs to slow or stop the progression of the disease.

The current best estimate is that more than 200,000 Australians live with Parkinson’s in Australia, with nearly 40 people diagnosed every day. Those figures are forecasted to double in the next 15 years. The exact number of people with Parkinson’s is not known as there is no clinical diagnostic test.

In a team effort spanning both the Bahlo and Dewson labs from the Parkinson’s Disease Research Centre as well as WEHI’s Human-based Research and Clinical Trials group and WEHI Research Computing, researchers led by Professor Melanie Bahlo and Dr Fei Wang discovered a new link between blood immune cells and Parkinson’s disease.

The finding brings the team a critical step closer to a blood test that could be used for diagnosing and monitoring the progression of the disease.

“The ultimate goal is to be able to screen for Parkinson’s disease in a similar way to the national screening program for bowel cancer, so people can get access to medication sooner,” Prof Bahlo said.

Mitochondrial dysfunction has long been associated with Parkinson’s disease and a potential biomarker that has emerged for measuring mitochondrial health is counting the ‘mitochondrial DNA copy number’,or mtDNA-CN.

But the new study, published in NPJ Parkinson’s Disease, suggests the link between mtDNA-CN and Parkinson’s disease may not stem from mitochondrial dysfunction, as previously thought.

Mitochondria are the sources of cellular energy and have their own DNA that is different to nuclear DNA. Cells have multiple mitochondria, each with multiple copies of mitochondrial DNA. Some cells, like those found in the heart, need lots of mitochondria whereas others need far fewer.

With mitochondrial dysfunction known to play a major role in Parkinson’s disease, previous thinking was that the number of mitochondrial DNA copies in blood samples could be used as a biomarker.

Because it is virtually impossible to count the exact number of mitochondrial DNA copies, the WEHI team developed a software algorithm to estimate the count from a DNA sequencing method using blood samples, testing it initially on a dataset of over 10,000 participants.

They discovered that lower levels of mitochondrial DNA in the blood are not directly linked to an increased risk and severity of Parkinson’s disease, as was previously thought. This apparent connection vanished when the team considered the different types of cells present in the blood.

They instead found a stronger link with certain immune cells, specifically neutrophils and lymphocytes, which are types of white blood cells.

This suggests that the previously reported relationship between mtDNA–CN and Parkinson’s is linked by immune responses in blood, instead of mitochondrial dysfunction.

White blood cells are related to blood immune and inflammation responses. It is known that people with Parkinson’s disease show elevated levels of neuroinflammation.

Building on their findings, the researchers replicated their study using the UK Biobank, analysing data from nearly 500,000 participants, making it the most extensive study of mtDNA-CN in Parkinson’s so far.

This replication confirmed their results, highlighting the reliability of their methodological framework.

The researchers have made the specialised software they developed for estimating mtDNA-CN, called mitoCN, freely available for use by teams around the world, to drive forward studies beyond Parkinson’s disease.

In 2023 the Michael J. Fox Foundation announced a newly identified biomarker that relies on spinal fluid to test for the presence of alpha-synuclein. Because the test requires an invasive spinal tap, it has inherent restrictions.

“A blood test, on the other hand, is far easier and cost-effective, making it more likely to be used by clinicians,” said Dr Fei Wang.

Biomarkers are not just important for diagnosing Parkinson’s. A blood biomarker also has the potential to be used to track disease progression so clinicians can adjust medications to help deliver a better quality of life, as well as measuring drug effectiveness during a clinical trial.

The research was funded by the Felton Bequest philanthropic donation as well as grants from the Michael J Fox Foundation, Shake It Up Foundation Australia and the NHMRC.