Scientists have identified a new method of testing allowing Parkinson’s disease to be defined earlier and more accurately, it was announced today.
Accurate biomarkers for Parkinson’s disease could also help clarify subtypes of the disease and improve clinical trials, researchers say.
Professor Andrew Siderowf of the University of Pennsylvania, USA, and colleagues write in The Lancet that the hallmark of Parkinson’s disease is the accumulation of misfolded, aggregated alpha-synuclein protein in the substantia nigra and other brain areas.
Recently, techniques developed to detect prion diseases have been used to detect this protein in Parkinson’s disease.
Now, Professor Siderowf’s team has tested the method more widely in an ongoing research cohort of Parkinson’s disease patients.
Samples of cerebrospinal fluid gathered from 1,123 participants were tested, including from non-disease manifesting carriers of genetic variants linked to Parkinson’s.
The test was highly accurate at showing which participants were manifesting the disease.
“This study represents the largest analysis of alpha-Syn-SAA for biochemical diagnosis of Parkinson’s disease,” the authors write. “Our results demonstrate that the assay classifies Parkinson’s disease patients with high sensitivity and specificity, provides information about molecular heterogeneity, and detects prodromal individuals prior to diagnosis.”
They conclude that alpha-Syn-SAA has a crucial role in therapeutic development, “both to identify pathologically defined subgroups of patients and to establish biomarker-defined at-risk cohorts”.
Professor Siderowf commented: “Identifying an effective biomarker for Parkinson’s disease pathology could have profound implications for the way we treat the condition.
Co-author Dr Luis Concha added: “Our results indicate that misfolded alpha-synuclein is detectable before dopaminergic damage in the brain is about to be observed by imaging, suggesting ubiquitous spread of these misfolded proteins before substantial neuronal damage has occurred.”
Siderowf, A. et al. Assessment of heterogeneity among participants in the Parkinson’s Progression Markers Initiative cohort using alpha-synuclein seed amplification: a cross-sectional study. Lancet 13 April 2023
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