The method is expected to diagnose the disease in the early stages, when treatment and intervention options are more effective, says researcher
An important advance in the early detection of Parkinson’s disease may improve the diagnosis and treatment of this neurodegenerative condition. Researchers published a study in the renowned scientific journal The Lancet Neurology describing an innovative technique capable of identifying the abnormal accumulation of proteins associated with Parkinson’s disease. This promising discovery can play a key role in the early diagnosis and clinical characterization of the disease.
The study was led by experts at the University of Pennsylvania Perelman School of Medicine and the Parkinson Progression Marker Initiative (PPMI). They investigated a method known as the α-synuclein protein amplification assay (αSyn-SAA). This technique was developed to identify misfolded aggregates of this protein, which are the pathological hallmark of Parkinson’s disease.
The study results confirmed that the αSyn-SAA assay can accurately detect the presence of the neurodegenerative disease. Furthermore, the method has the potential to identify at-risk individuals and detect early non-motor symptoms, even before formal diagnosis.
The innovative technique analyzed cerebrospinal fluid samples from 1,123 selected participants. These included individuals with a confirmed diagnosis of the disease, people at risk who had genetic variants related to the disease, and participants with non-motor symptoms, such as sleep disturbances or loss of smell, which may indicate an early stage of the disease.
The αSyn-SAA assay showed high accuracy in detecting the Parkinson’s disease biomarker, regardless of the clinical characteristics of the participants. The test yielded positive results in 88% of all diagnosed participants, including sporadic and genetic cases. In cases without a known genetic cause, 93% of individuals tested positive.
However, results have varied for people with genetic forms of Parkinson’s disease. Approximately 96% of people with the GBA variant tested positive, compared to 68% of people with the LRRK2 genetic variant.
Surprisingly, the majority of participants with non-motor symptoms also tested positive on the assay, indicating the presence of α-synuclein protein aggregates, even before formal diagnosis. These results suggest that the accumulation of these proteins may be a very early indicator of the onset of the disease.
Loss of Smell
One clinical feature that was proved to be highly predictive of positive outcomes is the loss of smell, one of the most common indicators in people without classic symptoms of Parkinson’s disease. Around 97% of the participants with loss of smell had positive test results, while only 63% of those who kept their sense of smell unchanged had positive results.
Tanya Simuni, one of the paper authors and a researcher at Northwestern University, highlights the importance of the discovery, stating that loss of smell appears to be a strong indicator of Parkinson’s disease. However, she notes that the study identified individuals with positive αSyn-SAA assay results who did not yet have measurable loss of smell, indicating that the presence of the misfolded α-synuclein protein may occur before the onset of olfactory symptoms.
Although the results are promising, it is important to highlight that the study only looked at patients at a specific point in time, and more research is needed to understand how the sense of smell may evolve over time and how this relates to the accumulation of smell aggregates. α-synuclein in the brain.
Additionally, researchers performed a postmortem analysis on 15 study participants who were diagnosed with Parkinson’s disease in life. Of the 14 cases that presented the typical pathology of the disease, all were positive in the new exam. Only one individual, who also had the LRRK2 genetic variant and had no changes in smell throughout his life, had a negative test result.
These promising results indicate that the αSyn-SAA assay may play a key role in the early diagnosis of Parkinson’s disease. Early detection would allow treatment to begin earlier, which could lead to better outcomes for patients. Furthermore, identifying different subsets of patients based on trial results could facilitate treatment personalization, offering more effective therapeutic approaches and accelerating clinical trials.
Andrew Siderowf, co-author of the study and professor at the Perelman School of Medicine at the University of Pennsylvania, highlights the importance of these findings for the medical field. “Recognizing the heterogeneity in the underlying pathology of Parkinson’s disease has been challenging, but identifying an effective biomarker, such as the αSyn-SAA assay, could have profound implications for the treatment of the disease,” he says.
Research has demonstrated that the technique is highly accurate in detecting Parkinson’s disease biomarkers, regardless of patients’ clinical characteristics. “With these advances, it is expected that it will be possible to diagnose the disease in its early stages, when treatment and intervention options are more effective,” says Siderowf.
The expert understands that, “although there is still much to be explored and researched, these discoveries represent an important step in understanding Parkinson’s disease and could pave the way for more effective diagnostic and treatment approaches. With more accurate and earlier detection, there is hope to improve patients’ quality of life and accelerate the development of innovative therapies to combat this neurodegenerative condition.”
The article “Assessment of heterogeneity among participants in the Parkinson’s Progression Markers Initiative cohort using α-synuclein seed amplification: a cross-sectional study” can be accessed here.