Blood analysis reveals signs of Parkinson's 10 years before diagnosis
In 2017, scientists at Columbia University found the first direct evidence that autoimmunity may play a role in the onset of Parkinson’s disease. The same team has been working to fill in this timeline of physiological events and uncovered further evidence of how the immune system contributes to the development of the disease, potentially opening up new windows of opportunity for early intervention.
Our body’s immune system does a mighty job of protecting us against foreign invaders like viruses, bacteria and cancer cells. Sometimes, however, it mistakes our own cells for harmful ones and launches attacks on healthy organs and tissues. This is the type of autoimmune response that can give rise to diseases such as rheumatoid arthritis and multiple sclerosis.
For quite some time, the Columbia University researchers have been exploring how autoimmunity could play a role in Parkinson’s disease and in 2014 published a study describing, for the first time, how dopamine neurons are susceptible to autoimmune attacks. The death or impairment of dopamine neurons is central to the onset of Parkinson’s, leading to the motor symptoms and cognitive decline associated with the disease.
The 2017 study showed how a damaged protein known as alpha-synuclein triggers this process, serving as a target for some types of T cells, which are central to the body’s immune response. In Parkinson’s patients, these proteins gather in clumps on brain cells that produce dopamine, which leads some T cells to mistake the brain cells for a threat and proceed to attack and kill them off.
For their latest study, the researchers teamed up with scientists at the La Jolla Institute for Immunology to trace this process back to its roots. The team collected blood samples from a large group of Parkinson’s patients and compared their T cells to a control group of healthy subjects. This revealed that the type of T cells that respond to the alpha-synuclein are most abundant when the patient is first diagnosed with Parkinson's, and then start to disappear as the disease progresses, with few exhibiting any at all 10 years later.
One of the Parkinson’s patients had blood samples going back long before they were diagnosed with the disease. In this case, the researchers’ analysis revealed a strong T cell response to alpha-synuclein 10 years prior to diagnosis, with the cells’ activity again fading as the disease progressed.
"This tells us that detection of T cell responses could help in the diagnosis of people at risk or in early stages of disease development, when many of the symptoms have not been detected yet," says study author Alessandro Sette. "Importantly, we could dream of a scenario where early interference with T cell responses could prevent the disease from manifesting itself or progressing."
The scientists point to existing therapies that can temper inflammation from these types of T cell reactions as a potential tool to intervene in this process. The findings also point to the possibility of monitoring T cells in at-risk patients to pick up and act on early signs of the disease. From here, the team hopes to study more Parkinson’s patients over longer periods to learn more about how the T cell response evolves over time.
"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,” says study author Professor David Sulzer. “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 10 years instead of a week."
The research was published in the journal Nature Communications.