Immune system activity could point the way to the development of Parkinson’s disease

Mitochondria auto reactivity in PD patients as a new biomarker for the disease

Diana Matheoud
Adjunct Professor
Université de Montréal
New Investigator Award
$90,000 over two years

Among the highest priorities of Parkinson’s disease research has been the development of a diagnostic test to indicate the onset of this condition, so that people could begin treatment as soon as possible. This goal depends on finding a specific biological marker for neurodegeneration, something that Diana Matheoud is attempting to pin down.

The adjunct professor at Université de Montréal has been exploring the unexpected participation of the body’s immune system in the development of Parkinson’s. Two well-studied genes, called PINK1 and Parkin, are already known to play a major part of this development. Only very recently, however, have they been linked with the regulation of the body’s immune response.

That discovery came when scientists tried to induce features of Parkinson’s in mice that had been genetically altered with the PINK1 mutation. Only in the wake of an infection did the symptoms of the disease begin to appear, an observation that led Matheoud to look more closely at the impact of that infection at the cellular level. She found that the presence of the invading bacterium altered a fundamental molecular pathway that cells typically use to identify this kind of threat.

Matheoud found the changes to this pathway, which is called antigen presentation, specifically affected the mitochondrion, a vital structure within every cell that is responsible for providing the energy to carry out all of the cell’s functions. Since the breakdown of mitochondria is a hallmark of Parkinson’s, evidence of this reaction to infection could well provide the crucial biomarker that would dramatically benefit patients by predicting the state and even the course of their disease. If researchers could develop a test that would indicate that reaction, it could alert doctors to the presence of Parkinson’s disease much earlier than the diagnoses happening now.

“We found that PINK1 and Parkin were very important for the protection of the antigen presentation from the mitochondria,” she says, referring to the mitochondrial antigen presentation as MitAP. “It’s a real connection between what we see with mitochondrial dysfunction and the stimulation of the immune system—this makes the perfect link between the two.”

She adds that the New Investigator Award from Parkinson Canada is enabling her to move this work from mice to the study of blood samples donated by human patients, which will begin early in 2019. This next phase of the research will look for the same immune system response that has already been confirmed in the animal model.

“If that is the case, it would mean MitAP is happening in humans and we have the link there, too,” Matheoud says.