The combined alpha-synuclein test may help diagnose and monitor Parkinson’s disease

Researchers have developed a test that may help diagnose more accurately Parkinson’s disease and monitor its progress. It combines two laboratory techniques already used to measure alpha-synuclein masses in cerebrospinal fluid (CSF).

Alpha-synuclein It is a protein that gradually accumulates to toxic levels in the brain and spinal cord of patients with Parkinson’s. Cerebrospinal fluid is the fluid that surrounds the brain and spinal cord. The test has been found to accurately distinguish Parkinson’s patients from healthy people and measure alpha-synuclein levels to determine disease severity.

The researchers noted that these findings suggest that the new test can be used not only to diagnose Parkinson’s disease, but also to monitor its progression and response to treatments.

The results are detailed in the study.Disease-associated alpha-synuclein aggregates as biomarkers for clinical stage of Parkinson’s diseasePosted in Neurology.

Usually Parkinson’s disease diagnosed After the onset of clinical symptoms, “but the neurodegenerative process is thought to have begun many years before overt clinical treatment.” symptoms Researchers wrote.

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Thus, disease biomarkers are needed to identify patients at risk, monitor disease progression, and differentiate Parkinson’s disease from other neurodegenerative conditions.

Because neuronal loss in Parkinson’s disease results primarily from toxic accumulation of unfolded α-synuclein clusters, the protein is an attractive target for diagnostic tests. A number of methods have been used to detect their masses in human tissues or fluids.

Enzyme-linked immunosorbent assay (ELISA) is a fast and sensitive antibody-based method for measuring protein levels, and can detect the amount of these masses, or oligomers. Therefore, he or she will likely monitor changes in these levels over time and after treatment.

However, the ‘diagnostic accuracy in distinguishing [Parkinson’s patients] of the controls were unsatisfactory,” the researchers wrote.

Meanwhile, the Seed Amplification Test (SAA) has been shown to be very sensitive in distinguishing between Parkinson’s patients, healthy people, and those with other diseases, which may allow a definitive diagnosis.

SAAs assess the seeding activity of a protein, or the rate at which a protein clumps together to form toxic aggregates. This involves introducing a small amount of the lab-made alpha-synuclein protein into a biological sample.

In diseases where alpha-synuclein aggregates, this lab-made protein will be recruited and fused into clumps, which can then be amplified and detected.

However, current SAAs’ are essentially binary tests (positive or negative) with only a semi-quantitative reading, which makes them suboptimal for monitoring longitudinal changes in blood levels. [alpha-synuclein] It accumulates over the course of the disease or in response to treatment,” the researchers wrote.

The common diagnostic test is more accurate

An international team of researchers investigated whether a combination of ELISA and SAA could provide an accurate reading of CSF alpha-synuclein clumps that could reflect disease severity in patients.

This approach used SAA to sensitively identify the presence of unfolded α-synuclein clumps, which can then be accurately quantified by ELISA.

First, they explored the potential of the test in brain tissue of people with Parkinson’s disease and dementia with Lewy bodies (DLB), Alzheimer’s disease, and from healthy subjects who acted as controls. DLB and Alzheimer’s are both neurodegenerative diseases, but only DLB is characterized by the accumulation of alpha-synuclein.

The combined approach was very sensitive in distinguishing between Parkinson’s and DLB patients, Alzheimer’s patients and healthy controls. It also allowed the detection of aggregates earlier than using SAA alone.

Next, the team evaluated the diagnostic efficacy of the combined test using cerebrospinal fluid samples from 62 Parkinson’s patients (58% of women), with a mean age of 57.5, and 34 age-matched healthy subjects (47% of women).

The results once again showed that the test could discriminate between people with and without Parkinson’s with high accuracy.

In addition, alpha-synuclein clumping levels measured with the combined approach were significantly associated with Parkinson’s disease severity, as assessed with the Standardized Parkinson’s Disease Rating Scale-Part III and the Hoehn and Yahr Scale. In contrast, when SAA was used alone, the results were not related to measures of clinical severity.

The observed association between pooled test readings and disease severity was confirmed in a second set of CSF samples—49 Parkinson’s patients (mean age, 64) and 48 age- and sex-matched healthy subjects.

The results were similar to those in the first group, again showing significant associations between test output and both measures of Parkinson’s disease severity.

The results generally support the combined ELISA-SAA test for the detection and severity of Parkinson’s disease.

“We have established and validated a new approach to provide clinical information about the underlying disease severity in affected patients [Parkinson’s]and thus potentially a promising tool to support clinical trial targeting [alpha-synuclein] totals in [Parkinson’s]The researchers wrote, noting that future studies that tested patients over time could reveal more about the potential of this approach.

Future research should also assess whether this combination approach is useful with other diseases associated with alpha-synuclein, and in testing therapies that target protein aggregation, they said.