Cerebrospinal fluid lipidomic fingerprint of obstructive sleep apnoea in Alzheimer’s disease

Springer Science and Business Media LLC - Tập 15 Số 1
Farida Dakterzada1, Iván D. Benítez2, Adriano Targa2, Anna Carnes1, Montse Pujol2, Mariona Jové3, Olga Mínguez2, Rafi Vaca2, Manuel Sánchez‐de‐la‐Torre4, Ferrán Barbé5, Reinald Pamplona3, Gerard Piñol‐Ripoll1
1Unitat Trastorns Cognitius, Cognition and Behaviour Study Group, Santa Maria University Hospital, IRBLleida, Rovira Roure No. 44, Lleida, 25198, Spain
2Group of Translational Research in Respiratory Medicine, Hospital Universitari Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain
3Department of Experimental Medicine, University of Lleida-Biomedical Research Institute of Lleida (UdL-IRBLleida), Lleida, Spain
4Department of Nursing and Physiotherapy, Group of Precision Medicine in Chronic Diseases, University Hospital Arnau de Vilanova and Santa María, IRBLleida, Faculty of Nursing and Physiotherapy, University of Lleida, Lleida, Spain
5Center for Biomedical Research in Respiratory Diseases Network (CIBERES), Madrid, Spain

Tóm tắt

Abstract Background Obstructive sleep apnoea (OSA) has a high prevalence in patients with Alzheimer’s disease (AD). Both conditions have been shown to be associated with lipid dysregulation. However, the relationship between OSA severity and alterations in lipid metabolism in the brains of patients with AD has yet to be fully elucidated. In this context, we examined the cerebrospinal fluid (CSF) lipidome of patients with suspected OSA to identify potential diagnostic biomarkers and to provide insights into the pathophysiological mechanisms underlying the effect of OSA on AD. Methods The study included 91 consecutive AD patients who underwent overnight polysomnography (PSG) to diagnose severe OSA (apnoea-hypopnea index ≥ 30/h). The next morning, CSF samples were collected and analysed by liquid chromatography coupled to mass spectrometry in an LC-ESI-QTOF-MS/MS platform. Results The CSF levels of 11 lipid species were significantly different between AD patients with (N = 38) and without (N = 58) severe OSA. Five lipids (including oxidized triglyceride OxTG(57:2) and four unknown lipids) were significantly correlated with specific PSG measures of OSA severity related to sleep fragmentation and hypoxemia. Our analyses revealed a 4-lipid signature (including oxidized ceramide OxCer(40:6) and three unknown lipids) that provided an accuracy of 0.80 (95% CI: 0.71–0.89) in the detection of severe OSA. These lipids increased the discriminative power of the STOP-Bang questionnaire in terms of the area under the curve (AUC) from 0.61 (0.50–0.74) to 0.85 (0.71–0.93). Conclusions Our results reveal a CSF lipidomic fingerprint that allows the identification of AD patients with severe OSA. Our findings suggest that an increase in central nervous system lipoxidation may be the principal mechanism underlying the association between OSA and AD.

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