Detection of alpha synuclein seeding activity in tear fluid in patients with Parkinson’s disease

AbstractDetection of alpha-synuclein seeding activity in tear fluid (TF) might provide a promising non-invasive biomarker for Parkinson’s disease (PD) diagnosis.In this study, we applied the alpha-synuclein seeding amplification assay (aSynSAA) to detect misfolded alpha-synuclein (aSyn) aggregation in TF from PD patients. The discovery cohort included 11 PD patients and 13 controls, and the validation cohort consisted of 9 PD patients and 11 controls without synucleinopathies.The aSynSAA yielded positive results in over 55% of PD patients. These findings were confirmed in a second cohort, including patients with prion diseases as a negative control for synuclein pathology. Our results demonstrate for the first time the ability of aSynSAA to distinguish between PD and control groups in TF, with PD showing the highest seeding activity compared to prion disease and control groups. Further comparisons between cerebrospinal fluid (CSF) and TF samples from the same individuals revealed consistent seeding results across both biofluids. These findings highlight the potential of tear fluid as a novel, accessible medium for detecting Lewy body-specific misfolded synuclein aggregation in PD, which could aid in early diagnosis and disease progression monitoring.