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. 2025 Feb 4:18:1609-1621.
doi: 10.2147/JIR.S475776. eCollection 2025.

Inflammatory and Redox Blood Gene Expression Fingerprint of Severe Obstructive Sleep Apnoea in Patients With Mild Alzheimer's Disease

Leila Romero-ElKhayat  1 , Farida Dakterzada  1 , Raquel Huerto  1 , Anna Carnes-Vendrell  1 , Olga Mínguez  2 , Montserrat Pujol Sabaté  2 , Adriano Targa  3   4 , Ferran Barbé  3   4 , Elena Milanesi  5   6 , Maria Dobre  5 , Gina Manda  5 , Antonio Cuadrado  5   7   8   9   10 , Gerard Piñol-Ripoll  1   11
Affiliations

Inflammatory and Redox Blood Gene Expression Fingerprint of Severe Obstructive Sleep Apnoea in Patients With Mild Alzheimer's Disease

Leila Romero-ElKhayat et al. J Inflamm Res. .

Abstract

Introduction: Obstructive sleep apnoea (OSA) is the sleep disorder most frequently found in patients with Alzheimer's disease (AD). The intermittent hypoxia (IH) caused by OSA may participate in AD pathogenesis through increase in oxidative damage and inflammation. We aimed to identify inflammatory and redox genes differentially expressed in the blood from AD patients with severe OSA compared with those with nonsevere OSA.

Methods: We included 40 AD patients diagnosed based on clinical manifestations and AD biomarker levels in cerebrospinal fluid (CSF). Severe or nonsevere OSA (apnoea-hypopnea index ≥ 30/h and < 30/h, respectively) was diagnosed through overnight polysomnography (PSG). The expression levels of 136 inflammation-related and 84 redox-related genes were evaluated by whole blood targeted transcriptomics.

Results: Three inflammatory and six redox genes were upregulated in the blood of AD patients with severe OSA. Three of them correlated with PSG parameters. A pathway enrichment analysis showed a strong enrichment of the serotonergic synapse pathway in severe OSA AD patients.

Discussion: Our results show an upregulation of nine genes involved in NF-κB-mediated inflammation and redox metabolism in the blood of patients with mild AD with severe OSA. Therefore, severe OSA may worsen the inflammation and oxidative damage that are already altered in patients with AD.

Keywords: Alzheimer’s disease; NF-κB signaling; gene expression; inflammation; obstructive sleep apnea; oxidative stress.

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Conflict of interest statement

The authors declare no competing interests in this work.

Figures

Figure 1
Figure 1
Means and standard deviations between OSA severity groups in AD patients in statistically significant differentially expressed genes.
Figure 2
Figure 2
Statistically significant correlations between differentially expressed genes, AHI and the arousal index after adjusting for age and sex. Blue dots: nonsevere OSA patients; red dots: patients with severe OSA.
Figure 3
Figure 3
Pathway analysis of differentially expressed genes (FC ≥ 1.5 and p values < 0.05).
See this image and copyright information in PMC

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