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Sleep and Breathing

, Volume 23, Issue 1, pp 251–257 | Cite as

Proteomic biomarkers of cognitive impairment in obstructive sleep apnea syndrome

  • Chitra LalEmail author
  • Gary Hardiman
  • Suchit Kumbhare
  • Charlie Strange
Sleep Breathing Physiology and Disorders • Original Article
  • 221 Downloads

Abstract

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.

Keywords

Cognitive impairment Proteomics Biomarkers Obstructive sleep apnea syndrome Menopause 

Abbreviations

OSAS

Obstructive sleep apnea syndrome

CI

Cognitive impairment

SCOR

Specialized center of research

HRT

Hormone replacement therapy

MCFSI

Mail-In Cognitive Function Screening Instrument

AUC

Area under the curve

STRING

Search Tool for the Retrieval of Interacting Genes/Proteins

BMI

Body mass index

AD

Alzheimer’s disease

IL1B

Interleukin-1 beta

ELAM-1

Endothelial-leukocyte adhesion molecule 1

CTSB

Cathepsin B

APP

Amyloid precursor protein

Notes

Funding

The SCOR study was funded by NIH grant UL1 RR029882 via the SCOR P50 grant mechanism.

Compliance with ethical standards

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

Dr. Lal has received grant support from Jazz pharmaceuticals and Invado pharmaceuticals and is a consultant for Jazz and Cipla pharmaceuticals. Drs. Strange, Hardiman, and Suchit Kumbhare have nothing to disclose.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Chitra Lal
    • 1
    Email author
  • Gary Hardiman
    • 2
  • Suchit Kumbhare
    • 1
    • 3
  • Charlie Strange
    • 1
  1. 1.Pulmonary, Critical Care, Allergy and Sleep MedicineMedical University of South CarolinaCharlestonUSA
  2. 2.MUSC Bioinformatics, Center for Genomics MedicineMedical University of South CarolinaCharlestonUSA
  3. 3.Medical University of South CarolinaCharlestonUSA

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