Detection of α-synuclein seeding activity in tear fluid as a candidate biomarker for Parkinson's disease

Abstract

Background Parkinson's disease (PD) is an α-synucleinopathy, and pathological α-synuclein (α-Syn) is detectable in peripheral tissues and fluids. However, the diagnostic utility of tear fluid as a minimally invasive source for α-Syn seed detection remains unclear. We aimed to detect α-Syn seeds in tear fluid and evaluate the clinical characteristics of α-Syn-positive patients. Methods Tear fluid was collected bilaterally using Schirmer strips. The α-Syn seeding amplification assay (αSynSAA) was performed using the real-time quaking-induced conversion (RT-QuIC) protocol. We analyzed 55 patients with PD and 40 control participants. Results The αSynSAA revealed α- synuclein seeding activity in tear fluid, showing 52.7% sensitivity and 100% specificity. αSyn SAA-positive patients had higher Movement Disorder Society–Unified Parkinsons Disease Rating Scale part III scores than αSyn SAA-negative patients. α-Syn seeding activity was detected in tear fluid from some patients with PD but not in disease controls. Conclusion This study demonstrates the feasibility of αSynSAA analysis in tear fluid, highlighting its potential as a novel substrate for biomarker development. Further studies in related synucleinopathies and in early or prodromal PD are needed to validate these findings and assess the diagnostic performance of this tear-based assay.