Study Rationale: REM sleep behavior disorder is well recognized as a prodromal condition associated with a high risk of subsequently developing neurodegenerative disorders termed synucleinopathies, including Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). The overarching goal of the North American Prodromal Synucleinopathy (NAPS) Consortium is to facilitate neuroprotective clinical trials to delay or prevent synucleinopathies, based on detailed characterization of REM sleep behavior disorder in a prodromal patient population.
Hypothesis: We hypothesize that detecting alpha-synuclein aggregates in a seed amplification assay in individuals with REM sleep behavior disorder, along with co-pathology markers in spinal fluid and blood and neuroimaging markers of neurodegeneration, will facilitate predicting conversion from the early prodromal disease stage to more obvious symptoms of more advanced PD.
Study Design:We will conduct seed amplification assays that measure aggregation of the brain protein alpha-synuclein, and we will perform a comprehensive array of blood, spinal fluid and brain imaging tests. We will then analyze how these test results relate to each other, and to the progression of PD symptoms in individuals with REM sleep behavior disorder, a neurologic condition characterized by dream enactment and known to be a strong risk factor for developing PD.
Impact on Diagnosis/Treatment of Parkinson’s disease: Successful completion of this study will advance the field by establishing a better understanding of how molecular tests of spinal fluid and blood, along with brain imaging tests, can be integrated with clinical symptoms and genetics to better predict an individual’s risk of developing PD and related illnesses.
Next Steps for Development: Next steps will include implementing a multi-component signature of blood, spinal fluid and brain imaging tests for use in clinical trials of disease-modifying therapies aimed at slowing the development and progression of PD and related neurodegenerative disorders.