Every day, 50 Australians are diagnosed with Parkinson’s disease — a progressive neurological condition that affects over 150,000 people across the country. While its exact cause remains unknown, a growing body of research suggests our immune system may play a far more critical role than previously thought.
Now, scientists have discovered a new clue: a surge in certain immune cells, called T cells, may occur years before the onset of physical symptoms. This finding could pave the way for earlier diagnosis and potentially better outcomes for patients.
Parkinson’s disease is best known for affecting movement. Tremors, stiffness, and difficulty with coordination often mark its later stages, as nerve cells in parts of the brain deteriorate. But what initiates that deterioration?
The lab of LJI Professor Alessandro Sette, Dr.Biol.Sci., has been investigating the role of the immune system, specifically T cells, a type of white blood cell that usually helps the body fight infection. However, when overactive or misdirected, T cells can cause harm, contributing to autoimmune diseases such as type 1 diabetes and rheumatoid arthritis.
Sette and his team previously found that people with Parkinson’s often have T cells that react to two key proteins found in vulnerable brain cells: alpha-synuclein and PINK1. These proteins are known to clump abnormally in Parkinson’s, damaging neurons.
But there was a missing piece: timing. Did T cells start reacting after the brain was already in decline, or were they contributing to the damage early on?
“We can see these reactive T cells in people after they develop Parkinson’s, but what happens before that?” says Emil Johansson, a researcher in the Sette Lab and co-author of the study.
Now, in their latest study, Sette and colleagues tracked T cell activity in individuals at high risk of developing Parkinson’s. These participants carried genetic risk factors or displayed early warning signs like disrupted sleep and loss of smell, often associated with the “prodromal” phase — the years before a Parkinson’s diagnosis.
Using a technique called Fluorospot to analyse blood samples, the researchers found that T cells reactive to alpha-synuclein and PINK1 were at their highest levels before diagnosis. In fact, T cell reactivity to PINK1 peaked during the prodromal stage, well before visible motor symptoms began.
“You can see that T cell reactivity before diagnosis,” Sette says. “This T cell immunity could be a marker for early Parkinson’s treatment, even before people show symptoms. And there’s reason to think that treating Parkinson’s in the very early stages can lead to a better outcome.”
Still, he urges caution. While the findings are compelling, they don’t yet prove that T cells cause Parkinson’s. It’s unclear whether the immune response is driving the disease — or reacting to brain changes already underway.
“Parkinson’s disease is associated with the destruction of nervous system cells,” explains Sette. “Does that destruction cause autoimmunity — or is the autoimmunity the cause of the disease? That’s the chicken-and-the-egg of inflammation in Parkinson’s disease.”
The researchers are now exploring whether some T cells could play a protective role. While certain T cells might worsen inflammation, others could help dampen it and protect brain tissue.
“We want to see if there are specific T cells that are protective,” says Johansson. “Could they interfere in inflammation and maybe reduce the number of autoimmune T cells?”
These findings are published in npj Parkinson’s Disease.