Longitudinal In Vivo Mapping of Alpha-Synuclein Aggregation in Parkinson’s Disease Using rNOE Imaging

Motivation: To develop a marker of protein aggregation in Parkinson's disease (PD), where alpha-synuclein deposition and aggregation contribute to neurodegeneration and disease progression. Goal(s): To investigate whether longitudinal rNOE changes follow the dynamics of protein aggregation in a PD mouse model with gut-initiated alpha-synuclein pathology. Approach: Longitudinal rNOE imaging was conducted at 6, 9, and 12 months. Mapping of rNOE signals was performed over time as the pathology advanced from the gut to the brain. Results: Elevated rNOE signals were observed in brain regions impacted by PD pathology, particularly hindbrain and midbrain, interpreted as an increase in protein aggregation that correlates with disease advancement. Impact: rNOE imaging has potential as a surrogate biomarker for protein aggregation changes associated with Parkinson's disease (PD) progression. This methodology has the potential to guide the development of therapies targeting protein aggregation, advancing neuroprotective strategies and disease management in PD.