This study will be observational and have a prospective case-control longitudinal design. Eligible subjects with idiopathic REM behavior disorder (RBD), Parkinson's disease with RBD, and healthy controls will be recruited. Subjects will undergo a sleep study to determine eligibility for the study and then in the study will undergo clinical assessments, including cognitive, sensory and motor clinical assessment, dopamine transporter scanning, and smell testing. Eligible subjects will undergo phlebotomy, lumbar puncture, stool and saliva collection, and genome-wide association scans at baseline and then undergo yearly sensory and motor clinical assessment to assess for phenoconversion to neurodegenerative disease. From blood and CSF samples, investigators will isolate mononuclear cells, and using cell immunologic and single cell genomic procedures, will look for the presence of T cells which autoreact with alpha-synuclein. Investigators will also look for the presence of increased clonality of T cells reflecting increased immune cell activation and the presence of cross reactivity of anti-alpha-synuclein T cells with microbial agents from subject gut stool samples.
The primary objective of this study is to determine whether T cell-mediated autoimmunity initiates the neurodegenerative process in PD, and if these early immunological processes converge on classic archetypes of neurodegeneration. Secondary objectives of this study are to determine to what extent the T cell-mediated autoimmune process initiates in the gut microbiome; and whether or not different PD- related genes or HLA type are associated with the presence of T cell-mediated autoimmunity. Investigators hypothesize that progression of Parkinson's Disease (PD) pathology is initiated and/or abetted by an autoimmune process involving alpha-synuclein-specific T cell activation triggered by gut microbiome dysbiosis, followed by neuro-immune interactions that establish PD in the brain. Investigators propose to address this hypothesis by integrating neuroimmunology, single cell genomics, mouse models, and microbiome approaches.
Study Type
OBSERVATIONAL
Enrollment
94
Yale New Haven Hospital
New Haven, Connecticut, United States
Characterization of of T cells
Number and types of T cells which autoreact to alpha- synuclein in the blood and cerebral spinal fluid (CSF)
Time frame: 2 months
Presence of increased clonality of T cells
The presence of increased clonality of T cells reflecting increased immune cell activation will be assessed in Mononuclear cells (PBMCs) and nucleated cells in the CSF isolated and prepared for single cell RNA sequencing.
Time frame: 2 months
presence of cross reactivity of anti-alpha- synuclein T cells
Presence of cross reactivity of anti-alpha- synuclein T cells with microbial agents from subject gut stool samples using cells isolated and prepared for single cell RNA sequencing.
Time frame: 2 months
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