NOVEL research proposes a shift from clinical to biological definitions for Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), suggesting the adoption of a neuronal α-synuclein (n-αsyn) disease framework and a new integrated staging system. This major change aims to redefine both conditions by focusing on the pathological detection of misfolded α-synuclein in cerebrospinal fluid (CSF) rather than on clinical symptoms alone.
Currently, PD and DLB are diagnosed based on clinical features, with α-synuclein pathology being the gold standard for confirmation. Recent advances in biomarker technology, particularly the seed amplification assay, enable the detection of pathological n-αsyn in living individuals, which could lead to an earlier and more precise diagnosis. This study proposes that n-αsyn disease, marked by the presence of pathological n-αsyn in the body, should replace the existing clinical syndromes. The researchers outline a new diagnostic system based on biological anchors: S, which signifies the presence of pathological n-αsyn, and D, representing dopaminergic neuronal dysfunction. The neuronal α-synuclein disease integrated staging system (NSD-ISS) identifies several stages, starting from no symptoms (stage 0) to increasing functional impairments (stages 2B–6), linked to the presence of n-αsyn and dopaminergic dysfunction.
This biological definition and staging framework offer significant potential for advancing research and early-stage interventional trials. However, while it promises more accurate disease detection and monitoring, the NSD-ISS is currently intended for research purposes only, as its use in clinical practice remains premature. Future developments in biomarkers and data-driven definitions of functional impairment could refine the staging system, enhancing its applicability. For clinical practice, these innovations may eventually guide earlier interventions, reducing disease progression in PD and DLB. Further validation is required before this system can be integrated into routine clinical settings.
Katrina Thornber, EMJ
Reference
Simuni T et al. A biological definition of neuronal α-synuclein disease: towards an integrated staging system for research. Lancet Neurol. 2024;23(2):178-90.
