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

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 h...

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Detalles Bibliográficos
Autores: Dakterzada, Farida, Benítez, Iván, Targa, Adriano, Pujol, Montserrat, Carnes Vendrell, Anna, Jové Font, Mariona, Minguez Roure, Olga, Vaca, Rafaela, Sánchez de la Torre, Manuel, Barbé Illa, Ferran, Pamplona Gras, Reinald, Piñol Ripoll, Gerard
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universitat de Lleida (UdL)
Repositorio:Repositori Obert UdL
OAI Identifier:oai:repositori.udl.cat:10459.1/464100
Acceso en línea:https://doi.org/10.1186/s13195-023-01278-7
https://hdl.handle.net/10459.1/464100
Access Level:acceso abierto
Palabra clave:Alzheimer’s disease
Biomarker
Cerebrospinal fluid
Diagnosis
Lipidomics
Obstructive sleep apnoea
STOP‑Bang questionnaire
Descripción
Sumario: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.