Mitochondrial dysfunction partly explained by immune responses
Study findings may lead to diagnostic testing based on blood samples
The number of copies of mitochondrial DNA in the blood of people with Parkinson’s disease are not a biomarker of poorly functioning mitochondria — the source of energy that powers cells — but may instead reflect immune responses that occur outside the brain, a study found.
The findings, which run counter to previous thinking, may mean it’s possible to develop minimally invasive tests using blood samples to diagnose Parkinson’s disease. The study, “Peripheral immune cell abundance differences link blood mitochondrial DNA copy number and Parkinson’s disease,” was published in npj Parkinson’s Disease.
While a recently identified biomarker can help detect Parkinson’s with high accuracy, the procedure requires an invasive spinal tap to draw a sample of spinal fluid. “A blood test … is far easier and cost-effective, making it more likely to be used by clinicians,” said Fei Wang, PhD, a researcher at The Walter and Eliza Hall Institute of Medical Research (WEHI) in Australia and the study’s first author, said in a WEHI news story.
“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,” said Melanie Bahlo, PhD, a researcher at the WEHI and the study’s lead author. Australia’s bowel cancer screening program uses a free, simple test that can be done at home.
Mitochondrial dysfunction plays an important role in Parkinson’s. Mitochondria are cellular structures crucial for energy production and have their own DNA. The mitochondrial DNA copy number, which reflects how intact mitochondria are, has been studied as a potential biomarker for Parkinson’s.
Large databases provide information
To study the link between mitochondrial DNA copy number and Parkinson’s risk, the researchers drew on data from two large databases, the Accelerating Medicines Partnership program for Parkinson’s Disease and the U.K. Biobank.
After adjusting for age, sex, and ancestry, they found that people with Parkinson’s had significantly lower mitochondrial DNA copy numbers in their blood than healthy individuals in both databases.
A lower mitochondrial DNA copy number was not only linked to a higher risk of Parkinson’s but also to more severe motor symptoms, reduced daily activity, and a weaker sense of smell. There was no consistent link with cognitive performance.
The team looked at the numbers of blood cells, which can affect mitochondrial DNA copy number. After adjusting for the numbers of each type of blood cell, the link between mitochondrial DNA copy number and the risk for Parkinson’s or more severe symptoms became weaker.
Further analysis using genetic data, called bidirectional Mendelian randomization, was used to test for a causal link between mitochondrial DNA copy number and Parkinson’s. However, there was no direct evidence that lower mitochondrial DNA copy number caused Parkinson’s. Instead, mitochondrial changes were more likely caused by other factors, such as inflammation, reflected by the number of blood immune cells.
The link was stronger when considering the present of neutrophils and lymphocytes, two types of white blood cells.
“Our findings indicate that blood [mitochondrial DNA copy number] is not a biomarker of mitochondrial dysfunction for [Parkinson’s] but confounds a potential immune signature which we were able to identify instead and which merits further investigation,” the researchers wrote.
About the Author
