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Alterations in Alzheimer’s Disease-Associated Gene Expression in Severe Obstructive Sleep Apnea Patients

Hsueh-Yu Li,M. Tsai,Chung-Guei Huang,Robert Y L Wang,L. Chuang,N. Chen,Chi-Hung Liu,Cheng-Ming Hsu,W. Cheng,Li-Ang Lee

Published 2019 in Journal of Clinical Medicine

ABSTRACT

Background: Obstructive sleep apnea (OSA) increases the risk of Alzheimer’s disease (AD), and inflammation may be involved in the early pathogenesis of AD in patients with OSA. However, the potential pathways between OSA and AD have yet to be established. In this study, we aimed to investigate differential expressions of AD-associated genes in OSA patients without evident AD or dementia. Methods: This prospective case-control study included five patients with severe OSA and five age and sex-matched patients with non-severe OSA without evident dementia who underwent uvulopalatopharyngoplasty between 1 January 2013 and 31 December 2015. The expressions of genes associated with AD were analyzed using whole-exome sequencing. Unsupervised two-dimensional hierarchical clustering was performed on these genes. Pearson’s correlation was used as the distance metric to simultaneously cluster subjects and genes. Results: The expressions of CCL2, IL6, CXCL8, HLA-A, and IL1RN in the patients with severe OSA were significantly different from those in the patients with non-severe OSA and contributed to changes in the immune response, cytokine–cytokine receptor interactions, and nucleotide-binding oligomerization domain-like receptor signaling pathways. Conclusions: Inflammation may contribute to the onset of AD and physicians need to be aware of the potential occurrence of AD in patients with severe OSA.

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