Identification of Oral Protein Biomarkers for Cognitive Impairment Susceptibility in Obstructive Sleep Apnea: A...

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a common sleep disorder, but cognitive impairment occurs only in a subset of patients, indicating individual susceptibility. This study aimed to identify oral fluid-derived protein biomarkers potentially related to neurobehavioral vulnerability in OSAHS by integrating clinical and animal model data. Nineteen participants (13 OSAHS, 6 controls) provided gingival crevicular fluid; age, body mass index (BMI), and weight showed no significant differences, while OSAHS patients exhibited significantly higher Epworth Sleepiness Scale (ESS) scores, reflecting increased daytime sleepiness. Fourteen C57BL/6J mice were randomly assigned to chronic intermittent hypoxia or normoxia conditions for 12 weeks; behavioral performance was evaluated using open field and Y-maze tests, and oral fluid was collected for proteomic analysis. 4D-DIA profiling identified 225 human and 105 mouse differentially expressed proteins; enrichment analysis highlighted humoral immunity and complement pathways. Notably, FN1 and JCHAIN were consistently upregulated across species, with expression changes accompanied by behavioral alterations in CIH mice. This clinic-driven, cross-species experimental study revealed FN1 and JCHAIN as shared, upregulated proteins potentially linked to hypoxia-associated neurobehavioral vulnerability in OSAHS. Rather than broadly focusing on differential expression, the study highlights these two proteins as candidates for further mechanistic investigation and future biomarker validation in cognitively vulnerable OSAHS patients.