Protein biomarker discovery for canine cognitive dysfunction syndrome based on molecular alterations observed in nasal fluids

Cognitive dysfunction syndrome (CDS) is characterized by mental – behavioral deterioration in elderly dogs and often acknowledged as a canine analog of neurodegenerative diseases (NDDs). A commonly shared feature among NDDs is the accumulation of toxic proteins within the brain and consequential degenerations. Several studies have suggested that such events in the brain can be reflected in the nasal area due to its anatomical and systemic adjacency. Furthermore, disease-specific profiles were identified in nasal-derived samples of patients of certain human NDDs, with credible diagnostic potential. Therefore, we hypothesized that alterations in CDS would be reflected in the nose and aimed to identify potential protein biomarkers based on nasal discharge from 65 individuals. Among the differentially expressed proteins within CDS, six marker candidates were selected and evaluated through quantitative proteomics. Two potential markers - CTSG and TRIM14 - showed high specificity with strong diagnostic capability, and both presented particularly high associations with the mild stage of CDS, posing potential links to its progression. Thus, this study presents CTSG and TRIM14 proteins as nasal-based potential biomarkers of CDS, suggesting a diagnostic alternative and a possible new approach to further define the disease based on its underlying pathology.