Parkinson’s disease biomarkers show high accuracy

Alpha-Synuclein Seed Amplification Assay (SAA) Accurately Detects Parkinson’s Disease in Cerebrospinal Fluid (CSF), Identifying People with Early Non-Motor Symptoms Before Diagnosis, Cross-sectional Data from the Parkinson’s Disease Progression Marker Initiative (PPMI)showed that.

The overall sensitivity for Parkinson’s disease was 87.7% and the specificity for healthy controls was 96.3%, reported Andrew Siderowf, MD, of the University of Pennsylvania, Philadelphia, and colleagues. lancet neurology.

In patients with sporadic Parkinson’s disease, the assay showed a sensitivity of 93.3%. For sporadic Parkinson’s disease with typical olfactory impairment, the sensitivity he had was 98.6%.

However, the results varied with the genetic form of Parkinson’s disease, with a sensitivity of 95.9%. obtain Mutation carrier and mutation carrier sensitivity 67.5% LRRK2. There were also differences by age and gender.

Misfolding of α-synuclein protein aggregates in the brain is a hallmark of Parkinson’s disease.Previous studies have shown that α-synuclein SAA Identifying people with Parkinson’s disease However, prior to this study, no large-scale analyzes addressing disease heterogeneity had been performed.

“Recognizing the heterogeneity of the underlying disease in people with Parkinson’s disease has been a major challenge,” Siderowf said in a statement.

“Identifying biomarkers that are effective in Parkinson’s disease pathology could have a significant impact on how Parkinson’s disease is treated, diagnosing people earlier and optimally treating different patient subsets.” It may be possible to identify methods and speed up clinical trials.

The 1,123 participants in this study included 545 with Parkinson’s disease (373 with sporadic disease, LRRK2 variants, and 49 obtain variant), 51 with prodromal Parkinson’s disease (18 with hyposmia, 33 with REM sleep behavior disorder), 310 asymptomatic carriers of Parkinson’s-related genes, had scans but evidence of dopamine deficiency 54 Parkinson’s disease patients without cancer and 163 healthy controls. Study participants were recruited between July 2010 and July 2019 and came from 33 participating academic neurology outpatient clinics worldwide.

Overall, 86% of prodromal participants had positive test results (44 of 51, 16 of 18 with hyposmia and 28 of 33 with REM sleep behavior disorder).Of the 310 asymptomatic carriers of Parkinson’s disease-related genes, 8% (9% LRRK2 and 7% obtain) was positive.

The clinical feature that most strongly predicted a positive outcome was loss of smell. Among Parkinson’s participants with anosmia, 97.2% tested positive, compared with 63.0% of those with no change in smell.

“Loss of smell appears to be a strong predictor of Parkinson’s disease, but this study identified individuals with positive alpha-synuclein SAA results but who had not yet lost their sense of smell.” It’s important to note that it existed long before our sense of smell was significantly lost,” said co-author Tanya Simuni, M.D., Ph.D., of Northwestern University in Chicago.

“Our study looked at patients only at a fixed time point, and we wanted to see how their sense of smell changed over time, and how this correlated with the accumulation of α-synuclein aggregates in the brain. Further research is needed to see if there is a connection,” she added.

Daniela Berg, M.D., Ph.D., and Christine Klein, M.D., Ph.D., Schleswig-Holstein University Hospital, Germany, said the findings confirm the high sensitivity and specificity of the α-synuclein SAA assay in distinguishing Parkinson’s disease patients from healthy controls. said. Accompanying editorial.

“But this study goes far beyond mere confirmation,” they wrote. “Siderowf et al. show that individuals with Parkinson’s prodromal symptoms who do not express the mutation exhibit abnormal α-synuclein aggregation prior to other detectable clinical or biomarker changes. This discovery lays the foundation for the biological diagnosis of Parkinson’s disease. comparable to Alzheimer’s diseaseuse of ATN [amyloid, tau, and neurodegeneration] Criteria allow diagnosis to be established before cognitive impairment is detected. ”

“This paradigm shift in diagnosis shifts the potential for therapeutic intervention to earlier stages of disease development,” added Berg and Klein. “Furthermore, nonmotor symptoms may represent different starting points for neurodegenerative processes, which may allow for future subtype-specific interventions.”

To exploit the potential of alpha-synuclein seed amplification, blood rather than CSF testing would be required, a viable and less invasive approach, the editors noted. “Although blood-based methods need to be further elaborated for scalability, alpha-synuclein SAA is a game changer in Parkinson’s disease diagnostics, research, and therapeutic trials,” they wrote.

Siderowf and co-authors acknowledge that the study had some limitations. Some participant groups had small sample sizes and analyzes were cross-sectional rather than longitudinal.