Profiling Tear Fluid in Prion Disease: A Pilot Proteomics Study

Abstract

Prion diseases are fatal neurodegenerative conditions with limited options for early diagnosis. Current biomarker strategies rely heavily on invasive sampling or are limited to symptomatic stages. Tear fluid (TF) offers a non-invasive, accessible biofluid that may reflect both systemic and neurodegenerative processes. In this study, we investigated the potential of TF proteomics to distinguish between healthy individuals, genetic prion mutation carriers, and patients with symptomatic prion disease, including Creutzfeldt-Jakob Disease (CJD) and Fatal Familial Insomnia (FFI).

Using mass spectrometry-based proteomics, distinct differences were observed in TF protein expression across the clinical spectrum. Pathway analysis revealed significant enrichment in immune-related and neurodegeneration-associated pathways, including Fc gamma R-mediated phagocytosis, NOD-like receptor signaling, and neurotrophin signaling. Additional alterations in actin cytoskeleton regulation, endocytosis, and tight junction pathways suggest broader involvement of cellular integrity and trafficking.

These findings support the feasibility of TF as a source of biomarkers for prion diseases, capturing both immune dysregulation and neuronal stress signatures. Importantly, TF profiles from healthy mutation carriers showed patterns that were intermediate between controls and symptomatic patients, raising the possibility of early or preclinical changes detectable in peripheral fluids.

This study highlights TF as a promising, underexplored medium for biomarker discovery in neurodegeneration. Its non-invasive nature and accessibility position it as a valuable tool for early detection, disease stratification, and longitudinal monitoring in prion disorders and potentially other neurodegenerative diseases.