Reduced viability and impaired activity of monocytes — a subset of immune cells that circulate in the blood — may contribute to the progression of Parkinson’s disease.
That discovery, by researchers from Aarhus University in Denmark, may further understanding of the underlying mechanisms involved in the development and progression of this complex disease.
“The research project confirms a growing theory that Parkinson’s disease is not only a brain disease, but is also connected with the immune system. Both in the brain and the rest of the body,” Marina Romero-Ramos, PhD, associate professor at Aarhus University and senior author of the study, said in a press release.
The study, “Alterations in Blood Monocyte Functions in Parkinson’s Disease,” was published in the journal Movement Disorders.
Parkinson’s disease is characterized by the accumulation of misfolded alpha-synuclein protein in the brain. This protein is toxic for brain cells, causing them to die and resulting in the characteristic motor symptoms associated with the disease.
However, the underlying mechanism that triggers this disease is not restricted to accumulation of alpha-synuclein. Indeed, growing evidence suggests that abnormal forms of the protein may originate in the gut, which then migrate to brain where it becomes toxic to brain cells.
These recent findings suggest that the immune system also may play a central role in this process, as circulating immune cells should be the first front to fight and destroy these potentially harmful abnormal proteins.
Researchers set up a new study to explore the role of circulating immune cells, in particular monocytes, in the development and progression of Parkinson’s disease.
Monocytes are a type of white blood cells that secrete several signaling molecules that are increased in Parkinson’s patients, and also are important mediators of the inflammatory response associated with diseases such as multiple sclerosis and stroke.
Researchers analyzed blood samples from 29 Parkinson’s patients and 20 age- and sex-matched volunteers without any sign of neurodegenerative disease.
Although at the time of sample collection no significant differences were observed between patients and controls, after culturing blood samples for two hours the team found that the count of viable cells was decreased significantly in female Parkinson’s patients compared to controls, with males showing a similar trend.
This reduction in viability also was observed in the number of monocytes, which were significantly lower in female patients than healthy female controls (5,780 vs. 12,813). This tendency also was observed in male patients (14,479 vs. 19,447).
In addition to the low viability of the cells, the team also found that monocytes of Parkinson’s patients were less responsive to stimuli. The cells showed less signs of activation when exposed to a pro-inflammatory chemical and to alpha-synuclein clumps.
“The lack of a response to stimulation suggests that the [Parkinson’s disease] patient cells are unresponsive and maybe even overstimulated, thus unable to respond to further stimulation,” the researchers wrote.
Further experiments revealed that monocytes from healthy volunteers secreted the signaling molecule IL-10 when in the presence of alpha-synuclein fibrils, while monocytes from Parkinson’s patients did not. This difference suggested that patients’ monocytes were unable to respond to alpha-synuclein stimulation, suggesting a differential activation and functional status of these cells.
“This knowledge may in the long term lead to the development of supplementary immune-regulating treatment being combined with the current medical treatment with the drug L-dopa, which only has an effect on the brain and the symptoms,” said Sara Konstantin Nissen, PhD, lead author of the study. “We believe such an additional drug might help to slow down the progression of the disease.”
These findings provide further support to the idea that Parkinson’s disease is more “than just a brain disorder,” which “requires a change of views among medical doctors and neurologists,” she said.