Evidence for immune changes in early Parkinson’s
Original articles:Lindestam Arlehamn, C. S., Dhanwani, R., Pham, J., Kuan, R., Frazier, A., Rezende Dutra, J., . . . Sette, A. (2020). alpha-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson’s disease. Nat Commun, 11(1), 1875. doi:10.1038/s41467-020-15626-w
20 April 2020
Immune cells responsive to alpha synuclein were found in two different groups of people with Parkinson’s, peaking in reactivity very close to the time of diagnosis. Findings from a case study suggest these may be present for several years prior to motor symptoms.
Why is it important?
These findings raise the possibility that these immune markers could help diagnose Parkinson’s earlier, opening up the possibility of earlier intervention for potential disease modification. They also highlight how central people with Parkinson’s are in moving science forward through their participation in research.
A major point of focus for clinicians and researchers working toward disease modifying interventions for Parkinson’s is to develop a sensitive and reliable way of picking up on changes that occur in the brain before the motor symptoms appear. This early period during which the condition is still in its very early stage is thought to be a critical window of opportunity for intervention. We know that problems such as REM sleep behaviour disorder, mood changes, loss of sense of smell and constipation often occur in the “prodromal” period that precedes a diagnosis of Parkinson’s, and reflect some of these early changes. But even before this, there is a “preclinical” phase during which these pathological processes are active but do not cause symptoms. How can we begin to understand and pick up on these events?
A study published in 2017 (see link below) by the team had found that in blood samples taken from people with Parkinson’s, compared to healthy controls, a particular type of immune cell (T cells) readily recognized and reacted to alpha synuclein, the protein which when misfolded causes damage to neurons. This is of great interest given all we know about the role of inflammation and autoimmunity in Parkinson’s. The group went on to build on this work, in a rare case study, as well as two different cohorts of people with Parkinson’s.
An individual who was diagnosed with Parkinson’s in 2009, had, for unrelated reasons, cryopreserved blood samples from 1998 to the present day. Having read the earlier published study, this individual donated her/his samples to the research team, who were able to examine how T cells were reacting to alpha synuclein over a period of almost 20 years. They were able to detect T cells reacting to alpha synuclein as early as 10 years before diagnosis. This reactivity was higher during the prodromal phase (1998-2006), compared to the period after diagnosis.
They then went on to investigate two cohorts of people with Parkinson’s, in whom T cell reactivity was again on average higher compared to controls. It was also higher close to the time of diagnosis, and declined thereafter. Out of the many different factors the investigated, reactivity was greater in older individuals, and those on lower medication doses, which is likely a reflection of early motor disease. To rule whether this was a general response to neurodegeneration rather than specific to Parkinson’s, the team also compared T cell reactivity from a group of people diagnosed with Alzheimer’s disease, to healthy controls, and found no difference.
It will be important to replicate these findings in larger population-based studies that track large numbers of people over longer time periods, focusing also on those with prodromal symptoms. These cohorts are not yet available, but they are recognized as being key to improving our understanding of the earliest phases of Parkinson’s.
Related work and trials
Lindestam Arlehamn, C. S., Dhanwani, R., Pham, J., Kuan, R., Frazier, A., Rezende Dutra, J., . . . Sette, A. (2020). alpha-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson’s disease. Nat Commun, 11(1), 1875. doi:10.1038/s41467-020-15626-w