Proteomic biomarkers of cognitive impairment in obstructive sleep apnea syndrome

• Published in: Sleep & breathing 2019-03, Vol.23 (1), p.251-257
• Main Authors: Lal, Chitra, Hardiman, Gary, Kumbhare, Suchit, Strange, Charlie
• Format: Article
• Language: English
• Subjects: Adiponectin; Adiponectin - blood; Angiopoietin; Angiopoietin-1 - blood; Apnea; Biomarkers; Biomarkers - blood; Blood Proteins - metabolism; Cathepsin B; Cathepsin B - blood; Ceruloplasmin; Ceruloplasmin - metabolism; Clinical trials; Cognitive ability; Cognitive Dysfunction - blood; Cognitive Dysfunction - diagnosis; Cohort Studies; Dentistry; Enzyme-linked immunosorbent assay; Female; Hormone replacement therapy; Humans; Insulin; Insulin - blood; Interleukin 1; Interleukin-1beta - blood; Internal Medicine; Medicine; Medicine & Public Health; Menopause; Middle Aged; Neurology; Neuropsychological Tests; Otorhinolaryngology; Pediatrics; Plasminogen Activator Inhibitor 1 - blood; Plasminogen activator inhibitors; Pneumology/Respiratory System; Proteins; Proteomics; Reference Values; Serine Endopeptidases - blood; Serum proteins; Sleep; Sleep apnea; Sleep Apnea, Obstructive - blood; Sleep Apnea, Obstructive - diagnosis; Sleep Breathing Physiology and Disorders • Original Article; Sleep disorders; Vascular diseases
• ISSN: 1520-9512; 1522-1709
• DOI: 10.1007/s11325-018-1693-8

Purpose There are currently no biomarkers that are associated with cognitive impairment (CI) in patients with obstructive sleep apnea syndrome (OSAS). This pilot study performed an exploratory plasma proteomic analysis to discover potential biomarkers and explore proteomic pathways that differentiate OSAS subjects with and without CI. Methods Participants were selected from a cohort of women within 5 years of menopause not on hormone replacement therapy between the ages of 45–60 years. The Berlin questionnaire was used to select OSAS participants who then completed the MCFSI (Mail-In Cognitive Function Screening Instrument) to measure cognition. Six subjects with the highest MCFSI scores (≥ 5 denoting CI) were compared to six with normal scores. Proteomic analysis was done by Myriad RBM using a targeted ELISA for 254 serum proteins. Pathway analysis of differentially expressed proteins was performed using STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) software. Results Distinct proteomic signatures were seen in OSAS subjects with CI as compared to those without CI. Proteins including insulin, prostasin, angiopoietin-1, plasminogen activator inhibitor 1, and interleukin-1 beta were overexpressed in OSAS subjects with CI. Proteins underexpressed in CI participants included cathepsin B, ceruloplasmin, and adiponectin. Pathway analysis revealed prominence of insulin-regulated vascular disease biomarkers. Conclusions Proteomic biomarkers in participants with cognitive impairment suggest roles for insulin, and vascular signaling pathways, some of which are similar to findings in Alzheimer’s disease. A better understanding of the pathogenic mechanisms of CI in OSAS will help focus clinical trials needed in this patient population.