Emerging evidence shows that a technique known as α-synuclein seed amplification assays (SAAs) has the potential to differentiate people with Parkinson’s disease from healthy controls.
Writing in the journal Lancet Neurology, a research team led by the University of Pennsylvania Perelman School of Medicine suggested that a positive result on αSyn-SAA may be an early indicator of disease onset and can detect at-risk individuals and those with early, non-motor symptoms of Parkinson’s prior to diagnosis.
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How It Works
SAAs is a laboratory method used to detect and measure the presence of abnormal clumps of protein in brain tissue samples. Scientists start by extracting a small amount of α-synuclein “seeds” from the samples. They introduce the seeds into a test tube containing other compounds that promote the growth and spread of α-synuclein clumps. By monitoring the growth of these clumps over time, scientists can determine the severity of α-synuclein-related brain disorders like Parkinson’s and evaluate the effectiveness of potential treatments.
This study analyzed SAAs of 1123 people over a decade. Subjects included people with Parkinson’s, healthy controls, people with scans that showed no signs of Parkinson’s, people diagnosed with prodromal Parkinson’s, and those who were carriers of a Parkinson’s gene but did not have symptoms.
Accuracy of Results
The test had nearly an 88 percent sensitivity for detecting Parkinson’s disease and 96 percent specificity for ruling out the disease in healthy people. But the clinical feature that most strongly predicted a positive αSyn-SAA result was loss of smell – one of the most common symptoms in prodromal people and those with a Parkinson’s diagnosis. In this population, the results were close to perfect accuracy (98.8 percent.)
The analysis was also good at identifying individuals with positive αSyn-SAA results, but who had not yet lost their sense of smell, the researchers pointed out. This, they said, indicated that α-synuclein pathology may be present even before patients realize a measurable loss of this sense.
However, the test proved less sensitive in subgroups where participants had a specific genetic mutation. Among people with a risk of developing Parkinson’s, the test was positive in most people with a certain sleep disorder or loss of smell and a small proportion of carriers of a Parkinson’s gene without symptoms.
“Our findings suggest that the αSyn-SAA technique is highly accurate at detecting the biomarker for Parkinson’s disease regardless of the clinical features, making it possible to accurately diagnose the disease in patients at early stages,” said study co-lead author Luis Concha, director of research and development at the biotech company, Amprion.
“Moreover, our results indicate that misfolded α-synuclein is detectable before dopaminergic damage in the brain is about to be observed by imaging, suggesting ubiquitous spread of these misfolded proteins before substantial neuronal damage has occurred,” she added.
Overcoming Challenges
Co-lead author Professor Andrew Siderowf, a Penn researcher and Parkinson Progression Marker Initiative investigator, explained that recognizing heterogeneity in underlying pathology among patients with Parkinson’s disease has been a major challenge.
“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,” Siderowf said.
The new study is the largest analysis of the diagnostic performance of αSyn-SAA for Parkinson’s disease to date. Previous research showed how the procedure distinguished clearly between individuals with Parkinson’s and people without the condition. But this study was larger in scale and included a much broader range of carefully described participants.
Finding out how olfactory levels change over time and how this relates to the build-up of a-synuclein aggregates in the brain will be the next step, the researchers said. They also plan longer-term trials to further investigate differences in αSyn-SAA results between people with different genetic forms of Parkinson’s.
