In a new study, researchers add increasing evidence that Parkinson’s disease is partly an autoimmune disease.
They report that signs of autoimmunity can appear in Parkinson’s disease patients years before their official diagnosis.
The research could make it possible to someday detect Parkinson’s disease before the onset of debilitating motor symptoms—and potentially intervene with therapies to slow the disease progression.
The research was conducted by scientists at the La Jolla Institute for Immunology (LJI) and elsewhere.
Scientists have long known that clumps of a damaged protein called alpha-synuclein build up in the dopamine-producing brain cells of patients with Parkinson’s disease.
These clumps eventually lead to cell death, causing motor symptoms and cognitive decline.
A 2017 study led by the team was the first to show that alpha-synuclein can act as a beacon for certain T cells, causing them to mistakenly attack brain cells and potentially contribute to the progression of Parkinson’s.
This was the first direct evidence that autoimmunity could play a role in Parkinson’s disease.
The new findings shed light on the timeline of T cell reactivity and disease progression.
The researchers looked at blood samples from a large group of Parkinson’s disease patients and compared their T cells to a healthy, age-matched control group.
They found that the T cells that react to alpha-synuclein are most abundant when patients are first diagnosed with the disease.
These T cells tend to disappear as the disease progresses, and few patients still have them ten years after diagnosis.
The researchers also did an in-depth analysis of one Parkinson’s disease patient who happened to have blood samples preserved going back long before his diagnosis.
This case study showed that the patient had a strong T cell response to alpha-synuclein ten years before he was diagnosed with Parkinson’s disease. Again, these T cells faded away in the years following diagnosis.
These findings show that detection of T cell responses could help in the diagnosis of people at risk or in the early stages of disease development when many of the symptoms have not been detected yet.
Importantly, early interference with T cell responses may help prevent the disease from manifesting itself or progressing.
The team says one of the most important findings is that the flavor of the T cells changes during the course of the disease, starting with more aggressive cells, moving to less aggressive cells that may inhibit the immune response, and after about 10 years, disappearing altogether.
It is almost as if immune responses in Parkinson’s disease are like those that occur during seasonal flu, except that the changes take place over ten years instead of a week.
The researchers hope to study more Parkinson’s patients and follow them over longer time periods to better understand how T cell reactivity changes as the disease progresses.
One author of the study is LJI professor Alessandro Sette.
The study is published in Nature Communications.
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