Biomarker Discovery in Parkinson’s Disease; A Focus on the Diagnostic Value of the Sphingolipid Pathway in Early-stage Diagnosis

This thesis investigates sphingolipid metabolism in Parkinson’s Disease (PD) patients and individuals at high risk of PD, rapid eye movement sleep behavior disorder (RBD) patients. Serum analysis of idiopathic PD patients revealed reduced sphingolipids linked to glucocerebrosidase (GCase) dysfunction. Sebum studies in RBD patients identified early sphingolipid alterations, including shifts in ceramides. Mouse models with GCase deficiency demonstrated region-specific disruptions in sphingolipid pathway flux. These findings underscore sphingolipid pathway alterations as promising diagnostic and therapeutic targets. Preliminary development of an in situ GCase assay lays the groundwork for future clinical applications to improve understanding and treatment of PD and RBD.