Immunologic and Imaging studies with TNF Therapy in Prodromal Synucleinopathies

REM sleep behavior disorder (RBD) is recognized as an early indicator of synucleinopathies such as Parkinson’s disease (PD), yet the mechanisms that drive the transition from prodromal symptoms to full disease remain poorly understood. Recent evidence suggests that inflammation mediated by tumor necrosis factor (TNF) may play a crucial role in this process, but direct clinical data connecting immune changes to disease progression in humans are limited. As a result, there is a pressing need to clarify how TNF-driven immune responses contribute to neurodegeneration and to identify strategies that could slow or prevent symptom onset in at-risk individuals. This project will investigate whether anti-TNF therapy with adalimumab can alter the course of prodromal synucleinopathies by integrating detailed immunophenotyping with advanced neuroimaging in individuals with RBD. By closely examining immune cell populations and brain changes before the development of PD or related disorders, the study aims to uncover the biological pathways linking inflammation to neurodegeneration. The findings could inform future interventions designed to delay or prevent motor and cognitive decline, ultimately advancing strategies for early treatment of neurodegenerative diseases.