A major study has confirmed the accuracy of a biochemical test for Parkinson’s and shown that it can identify the condition in people with early signs, who have yet to be diagnosed.
The largest study to date of the alpha-synuclein seed amplification assay (αSyn-SAA) confirms its validity as the first biological test to conclusively diagnose the disease in living people.
The breakthrough test, outlined in The Lancet Neurology, amplifies small quantities of misfolded α-synuclein protein deposits in cerebrospinal fluid so that it can be detected in the lab. The build-up of these abnormal aggregates in the brain is a hallmark of Parkinson’s disease.
Traditionally, clinical assessments and patient-reported outcomes have been used for Parkinson’s diagnosis or the disease has been identified through brain pathology.
Importantly, the likelihood of positive test results differed with disease subtypes and risk factors. This points to the test being able to distinguish both different underlying causes and potential response to treatment, making it of particular value to precision medicine.
“Identifying an effective biomarker for Parkinson’s disease pathology could have profound implications for the way we treat the condition, potentially making it possible to diagnose people earlier, identify the best treatments for different subsets of patients, and speed up clinical trials,” said co-lead author Andrew Siderowf, PhD, a professor at the University of Pennsylvania Perelman School of Medicine.
The findings come from a cross-sectional analysis of 1123 participants in the Parkinson’s Progression Markers Initiative (PPMI) study. These included people with Parkinson’s disease with and without associated genetic variants, healthy control individuals, and people at risk of developing the disease, either through early signs and symptoms or by virtue of being carriers of GBA and LRRK2 genetic variants.
Results showed that the assay had a sensitivity for Parkinson’s disease of 87.7% and specificity for healthy controls of 96.3%.
It accurately diagnosed Parkinson’s in 98.6% of people with loss of smell—which can be an early sign—who had sporadic disease, with no known genetic cause. Fewer positive results were seen among people with sporadic Parkinson’s who did not suffer smell loss, at 78.3%.
Positive results were also less common among people with Parkinson’s and a LRRK2 mutation, at 67.5% versus 95.9% in those with GBA.
Parkinson’s disease patients with the LRRK2 mutation and a normal ability to smell were even less likely to show positive assay results, at 34.7%, with this dropping even lower among women.
Among 51 people who were at-risk or had subclinical signs and symptoms such as rapid eye movement sleep behaviour disorder or loss of smell, 86.3% had a positive assay.
In a Comment article accompanying the study, Daniela Berg, PhD, and Christine Klein, PhD, from the University Hospital Schleswig-Holstein in Germany, said the test would have to use blood rather than cerebrospinal fluid in order to leverage its full potential—a less invasive approach that has proven to be viable.
“Although the blood-based method needs to be further elaborated for scalability, α-synuclein SAA is a game-changer in Parkinson’s disease diagnostics, research, and treatment trials,” they maintained.
In a statement, Kenneth Marek, PhD, PPMI principal investigator and president and senior scientist at the Institute for Neurodegenerative Disorders in New Haven, Connecticut, added: “Validation of this biomarker launches a new, biological era in Parkinson’s research.
“Using αSyn-SAA, we are already unlocking new understanding of Parkinson’s, which will transform every aspect of drug development and ultimately clinical care.”
