Autoimmunity in Parkinson's Disease
Is Parkinson's disease in part an autoimmune condition? Parkinson's is an age-related neurodegenerative condition in which the primary motor control symptoms result from the death of a specialized population of neurons that generate dopamine. There are also other harms done to neurological function, however. Under the hood, processes such as chronic inflammation, mitochondrial dysfunction, and aggregation of α-synuclein contibute to that cell death. Researchers here speculate on an autoimmune component to the pathology of Parkinson's disease, in that these mechanisms also drive the immune system into greater inflammatory activity that harms healthy tissue.
A new study adds increasing evidence that Parkinson's disease is partly an autoimmune disease. In fact, the researchers report that signs of autoimmunity can appear in Parkinson's disease patients years before their official diagnosis. 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.
An earlier study showed 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 performed 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. "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."
Therapies exist to treat inflammation from autoreactive T cells, and these TNF therapies are associated with lower incidence of Parkinson's disease. Going forward, the researchers are especially interested in using a tool called a T cell-based assay to monitor patients already at risk for Parkinson's to see if they could benefit from TNF therapies.