A technique that identifies the accumulation of abnormal deposits of proteins linked to the Parkinson’s disease can help with early detection and play a key role in the diagnosis and clinical characterization of the disease, according to research published in The Lancet Neurology.
The study’s findings confirm that the technique can accurately detect people with the neurodegenerative disease. It would also have the ability to identify at-risk individuals and those with early non-motor symptoms prior to diagnosis.
The method is technically known as the α-synuclein protein amplification assay (αSyn-SAA). The presence of misfolded aggregates of this protein in the brain is the pathological hallmark of Parkinson’s disease.
“Recognizing the heterogeneity in underlying pathology among patients with Parkinson’s disease has been a major challenge. Identifying an effective biomarker for the pathology of Parkinson’s disease could have profound implications for how we treat the disease, potentially making it possible to diagnose people earlier, identify the best treatments for different subsets of patients, and accelerate clinical trials.” Siderowf.
Siderowf, co-lead author of the study, is a professor at the Perelman School of Medicine at the University of Pennsylvania, in the United States, and an investigator for the Parkinson’s Progression Marker Initiative (PPMI).
The specialist says that the findings suggest that the technique is highly accurate in detecting the biomarker for Parkinson’s disease, regardless of clinical characteristics, making it possible to accurately diagnose the disease in patients in the early stages.
“In addition, our results indicate that misfolded α-synuclein is detectable before dopaminergic damage in the brain is about to be observed by imaging, suggesting the ubiquitous spread of these misfolded proteins before substantial neuronal damage occurs,” adds co-author of the study Luis Concha, director of research and development of Amprion, USA.
extensive analysis
The study is a comprehensive analysis of the diagnostic performance of the new technique for Parkinson’s disease.
Although previous research has shown that it can clearly distinguish between individuals with Parkinson’s disease and people without the disease, large-scale studies including a wide range of carefully described participants were lacking, the researchers said.
The authors evaluated the assay’s usefulness for detecting early signs of the disease using population-group data from the Parkinson’s Progression Markers Initiative (PPMI).
Among the 1,123 participants in the analysis were individuals with a confirmed diagnosis and people at risk who had two genetic variants (called GBA and LRRK2) linked to the disease.
We also included participants who had non-motor symptoms – such as sleep disturbances or loss of smell – that can be early signs of Parkinson’s disease, but had not been diagnosed and did not have any of the typical motor symptoms, such as tremors or muscle rigidity, which arise with the progression of the disease.
Samples of cerebrospinal fluid, which surrounds the brain and spinal cord, from each participant were analyzed. The innovative technique amplifies very small amounts of misfolded aggregates of the α-synuclein protein in samples from people with Parkinson’s disease to the point where they can be detected using standard laboratory techniques.
The results of the analyzes confirm that the new test identifies people with Parkinson’s disease with high accuracy, with positive results in 88% of all participants with diagnosis (combining sporadic and genetic cases).
In sporadic cases – those with no known genetic cause – 93% of subjects tested positive.
However, results varied for people with genetic forms of Parkinson’s disease, with 96% of people with the GBA variant testing positive, compared to 68% of people with the LRRK2 genetic variant.
Most participants with non-motor symptoms tested positive by the assay, indicating that they had protein aggregates, despite not yet being diagnosed with Parkinson’s.
According to the study, most participants with non-motor symptoms and a positive result had brain scans that did not show a decline in the expected number of dopamine-producing nerve cells – a biomarker signature that is present even before diagnosis.
This result suggests that the accumulation of α-synuclein protein aggregates may be a very early indicator of disease onset.
The clinical characteristic that most strongly predicted a positive result was the loss of smell – one of the most common symptoms in people still without classic signs and in those diagnosed with Parkinson’s disease.
Among all participants with Parkinson’s who had a loss of smell, 97% tested positive compared to 63% of those whose sense of smell remained unchanged.
“While loss of smell appears to be a strong predictor of Parkinson’s disease, it is important to note that this study identified individuals with positive αSyn-SAA results but who had not yet lost their sense of smell, indicating that α-synuclein pathology may be at risk. present even before there is a measurable loss of smell”, says study author Tanya Simuni, from Northwestern University, in the United States.
“Our study analyzed patients only at a fixed point in time, and more research is needed to find out how patients’ sense of smell may change over time and how this relates to the accumulation of a-synuclein aggregates in the brain.” .
Autopsy data from 15 participants, all diagnosed with Parkinson’s disease in life, showed that 14 had typical pathology and were positive in the new test. The only negative test case was an individual whose sense of smell remained unchanged in life and who also carried the LRRK2 variant.
Source: CNN Brasil

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