, and provides information on molecular subtypes, new research indicates.
“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,” the study’s co-lead author Andrew Siderowf, MD, of the University of Pennsylvania, Philadelphia, said in a news release.
“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,” added co-lead author Luis Concha-Marambio, PhD, director of research and development at Amprion, San Diego, Calif.
The study was published online in The Lancet Neurology.
‘New era’ in Parkinson’s disease
The researchers assessed the usefulness of αSyn-SAA in a cross-sectional analysis of 1,123 participants in the Parkinson’s Progression Markers Initiative (PPMI) cohort from 33 participating academic neurology outpatient practices in 12 countries.
The cohort included individuals with sporadic Parkinson’s disease from LRRK2 or GBA variants, healthy controls, individuals with clinical syndromes prodromal to Parkinson’s disease (rapid eye movement sleep behavior disorder [RBD] or hyposmia), and nonmanifesting carriers of LRRK2 and GBA variants. Cerebrospinal fluid (CSF) samples from each participant were analyzed using αSyn-SAA.
Overall, αSyn-SAA differentiated Parkinson’s disease from healthy controls with 87.7% sensitivity and 96.3% specificity.
Sensitivity of the assay varied across subgroups based on genetic and clinical features. Among genetic Parkinson’s disease subgroups, sensitivity was highest for GBA Parkinson’s disease (95.9%), followed by sporadic Parkinson’s disease (93.3%), and lowest for LRRK2 Parkinson’s disease (67.5%). Among clinical features, hyposmia was the most robust predictor of a positive assay result.
Among all Parkinson’s disease cases with hyposmia, the sensitivity of the assay was 97.2%, compared with 63.0% for Parkinson’s disease without olfactory dysfunction. Combining genetic and clinical features, the sensitivity of positive αSyn-SAA in sporadic Parkinson’s disease with olfactory deficit was 98.6%, compared with 78.3% in sporadic Parkinson’s disease without hyposmia. Most prodromal participants (86%) with RBD and hyposmia had positive αSyn-SAA results, indicating they had α-synuclein aggregates despite not yet being diagnosed with Parkinson’s disease.
Among those recruited based on their loss of smell, 89% (16 of 18 participants) had positive αSyn-SAA results. Similarly, in those with RBD, positive αSyn-SAA results were present in 85% of cases (28 of 33). No other clinical features were associated with a positive αSyn-SAA result.
In participants who carried LRRK2 or GBA variants but had no Parkinson’s disease diagnosis or prodromal symptoms (nonmanifesting carriers), 9% (14 of 159) and 7% (11 of 151), respectively, had positive αSyn-SAA results.
To date, this is the largest analysis of α-Syn-SAA for the biochemical diagnosis of Parkinson’s disease, the researchers said.
The results show that the assay classifies people with Parkinson’s disease with “high sensitivity and specificity, provides information about molecular heterogeneity, and detects prodromal individuals before diagnosis,” they wrote.
“These findings suggest a crucial role for the α-synuclein SAA in therapeutic development, both to identify pathologically defined subgroups of people with Parkinson’s disease and to establish biomarker-defined at-risk cohorts,” they added.
Amprion has commercialized the assay (SYNTap test), which can be ordered online.