Parkinson’s disease is a progressive neurological disorder affecting movement and cognition. Symptoms often overlap with other conditions, with up to 10% of patients misdiagnosed, impacting treatment and care.
Recently, a biomarker called the α-synuclein seed amplification assay (SAA), which detects the build-up and clumping of α-synuclein – a key protein in the brain linked to Parkinson’s disease – has shown promise for diagnosis. However, until now its effectiveness at distinguishing Parkinson’s disease from similar disorders, as well as its ability to predict disease progression in Parkinson’s disease, has been unclear.
The study, published in the Lancet Neurology, collected and analysed data from a total of 1631 participants, including those with Parkinson’s disease, progressive supranuclear palsy, and healthy controls enrolled in three cohorts. Baseline α-synuclein SAA data and follow-up clinical data were collected over a period of 13 years.
The researchers compared the seeding kinetics – how quickly and strongly the α-synuclein protein clumped together – in people with sporadic Parkinson’s disease, monogenic Parkinson’s disease, and progressive supranuclear palsy – a less common condition that shares similar symptoms with Parkinson’s disease.
The researchers found that α-synuclein SAA was positive in 96% people diagnosed with Parkinson’s disease in one of the cohorts, however they found that it was also positive in a small group of people with progressive supranuclear palsy. Investigating the seeding kinetics, the researchers found distinct patterns between the two patient groups, with those who had progressive supranuclear palsy showing slower and weaker clumping. This demonstrates the potential diagnostic value of the seeding kinetic measures over and above the binary version of the test.
They also found that those with GBA1-Parkinson’s disease, a genetic form of the condition, showed faster seeding kinetics than those with the more common, sporadic form. This is in line with GBA1-Parkinson’s disease being associated with faster progression.
Investigating the long-term outcomes in an international cohort, they found that faster seeding kinetics at baseline predicted cognitive decline in both sporadic and monogenic Parkinson’s disease. This was replicated in an independent cohort and highlights the prognostic value of the α-synuclein SAA kinetic measures in Parkinson’s disease.
Talking about the study, senior author Dr Edwin Jabbari, UCL Queen Square Institute of Neurology said:
For the first time, we show that differences in the aggressiveness of α-synuclein seeding can help distinguish Parkinson’s disease from similar conditions like progressive supranuclear palsy where α-synuclein occurs as a co-pathology. We also found that the α-synuclein seeding kinetics predict which Parkinson’s disease patients are more likely to experience cognitive decline. This opens the door to earlier and more accurate diagnosis and prognosis, and a refinement of clinical trial design.
