Study Rationale: The neuropathological hallmark feature of Parkinson’s disease (PD) is the accumulation of a misfolded protein called alpha-synuclein in neurons, which qualifies PD as a neuronal synucleinopathy. Following this observation and other advances in recent years, a biological definition and staging system for PD research, called NSD-ISS, has recently been proposed. Misfolded alpha-synuclein accumulates in other synucleinopathies, such as multiple system atrophy (MSA). In contrast to PD, alpha-synuclein accumulates mainly in glial cells in this rare disease, and its structure is distinct from that of PD.
Hypothesis: The project's overarching goal is to challenge the NSD-ISS classification by a well characterized cohort of subjects with MSA. Since PD and MSA have distinct synucleinopathy patterns, the NSD-ISS classification should give a distinct classification of both disorders.
Study Design: The project will leverage data and biofluid samples of the unique French MSA cohort launched in 2008. Cerebrospinal fluid samples will be used to determine alpha-synuclein seeding activity in MSA, PD and additional control groups before applying the NSD-ISS classification to MSA. In addition, potential associations between alpha-synuclein seeding activity, other biofluid markers, disease severity and progression will be determined.
Impact on Diagnosis/Treatment of Parkinson’s disease: The expected results will provide significant information to develop further/refine the NSD-ISS classification.
Next Steps for Development: Applying the NSD-ISS classification to additional synucleinopathy cohorts.