Dataset Information

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

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.

SUBMITTER: Li HY

PROVIDER: S-EPMC6780075 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Li Hsueh-Yu HY Tsai Ming-Shao MS Huang Chung-Guei CG Wang Robert Y L RYL Chuang Li-Pang LP Chen Ning-Hung NH Liu Chi-Hung CH Hsu Cheng-Ming CM Cheng Wen-Nuan WN Lee Li-Ang LA

Journal of clinical medicine 20190901 9

<h4>Background</h4>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.<h4>Methods</h4>This prospective case-control study included five patients with severe OSA and five age ...[more]

PMID: 31480626

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Project description:BackgroundObstructive sleep apnoea (OSA) is the most frequent form of sleep-disordered breathing in patients with Alzheimer's disease (AD). Available evidence demonstrates that both conditions are independently associated with alterations in lipid metabolism. However, it is unknown whether the expression of lipids is different between AD patients with and without severe OSA. In this context, we examined the plasma lipidome of patients with suspected OSA, aiming to identify potential diagnostic biomarkers and to provide insights into the pathophysiological mechanisms underlying the disease.MethodsThe study included 103 consecutive patients from the memory unit of our institution with a diagnosis of AD. The individuals were subjected to overnight polysomnography (PSG) to diagnose severe OSA (apnoea-hypopnea index ≥30/h), and blood was collected the following morning. Untargeted plasma lipidomic profiling was performed using liquid chromatography coupled with mass spectrometry.ResultsWe identified a subset of 44 lipids (mainly phospholipids and glycerolipids) that were expressed differently between patients with AD and severe and nonsevere OSA. Among the lipids in this profile, 30 were significantly correlated with specific PSG measures of OSA severity related to sleep fragmentation and hypoxemia. Machine learning analyses revealed a 4-lipid signature (phosphatidylcholine PC(35:4), cis-8,11,14,17-eicosatetraenoic acid and two oxidized triglycerides (OxTG(58:5) and OxTG(62:12)) that provided an accuracy (95% CI) of 0.78 (0.69-0.86) in the detection of OSA. These same lipids improved the predictive power of the STOP-Bang questionnaire in terms of the area under the curve (AUC) from 0.61 (0.50-0.74) to 0.80 (0.70-0.90).ConclusionOur results show a plasma lipidomic fingerprint that allows the identification of patients with AD and severe OSA, allowing the personalized management of these individuals. The findings suggest that oxidative stress and inflammation are potential prominent mechanisms underlying the association between OSA and AD.

Dataset Information

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

Publications

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

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