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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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
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spelling Cerebrospinal fluid lipidomic fingerprint of obstructive sleep apnoea in Alzheimer's diseaseDakterzada, FaridaBenítez, IvánTarga, AdrianoPujol, MontserratCarnes Vendrell, AnnaJové Font, MarionaMinguez Roure, OlgaVaca, RafaelaSánchez de la Torre, Manuel Barbé Illa, FerranPamplona Gras, ReinaldPiñol Ripoll, GerardAlzheimer’s diseaseBiomarkerCerebrospinal fluidDiagnosisLipidomicsObstructive sleep apnoeaSTOP‑Bang questionnaireBackground 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.Government of Catalonia, Department of Health (PERIS 2019 SLT008/18/00050), the Agency for the Management of University and Research Grants (2021 SGR 00761), and “Fundació La Marató TV3” (464/C/2014) to GPR. The Spanish Ministry of Science, Innovation, and Universities (Ministerio de Ciencia, Innovación y Universidades), co‑financed by FEDER funds from the European Union “A way to build Europe” (grant RTI2018‑099200‑B‑I00), the IRBLleida‑Diputació de Lleida (PIRS2021), and the Government of Catalonia: Agency for Management of University and Research Grants (2017SGR696) to RP. IRBLleida is a CERCA Program of the Government of Catalonia.BMC2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.1186/s13195-023-01278-7https://hdl.handle.net/10459.1/464100reponame:Repositori Obert UdL instname:Universitat de Lleida (UdL)Inglésinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-099200-B-I00Reproducció del document publica a: https://doi.org/10.1186/s13195-023-01278-7Alzheimer’s Research & Therapy, 2023, vol. 15, Article number 134cc-by (c) Authors, 2023Attribution 4.0 Internationalinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/oai:repositori.udl.cat:10459.1/4641002026-06-24T12:42:17Z
dc.title.none.fl_str_mv Cerebrospinal fluid lipidomic fingerprint of obstructive sleep apnoea in Alzheimer's disease
title Cerebrospinal fluid lipidomic fingerprint of obstructive sleep apnoea in Alzheimer's disease
spellingShingle Cerebrospinal fluid lipidomic fingerprint of obstructive sleep apnoea in Alzheimer's disease
Dakterzada, Farida
Alzheimer’s disease
Biomarker
Cerebrospinal fluid
Diagnosis
Lipidomics
Obstructive sleep apnoea
STOP‑Bang questionnaire
title_short Cerebrospinal fluid lipidomic fingerprint of obstructive sleep apnoea in Alzheimer's disease
title_full Cerebrospinal fluid lipidomic fingerprint of obstructive sleep apnoea in Alzheimer's disease
title_fullStr Cerebrospinal fluid lipidomic fingerprint of obstructive sleep apnoea in Alzheimer's disease
title_full_unstemmed Cerebrospinal fluid lipidomic fingerprint of obstructive sleep apnoea in Alzheimer's disease
title_sort Cerebrospinal fluid lipidomic fingerprint of obstructive sleep apnoea in Alzheimer's disease
dc.creator.none.fl_str_mv 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
author Dakterzada, Farida
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alzheimer’s disease
Biomarker
Cerebrospinal fluid
Diagnosis
Lipidomics
Obstructive sleep apnoea
STOP‑Bang questionnaire
topic Alzheimer’s disease
Biomarker
Cerebrospinal fluid
Diagnosis
Lipidomics
Obstructive sleep apnoea
STOP‑Bang questionnaire
description 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.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.1186/s13195-023-01278-7
https://hdl.handle.net/10459.1/464100
url https://doi.org/10.1186/s13195-023-01278-7
https://hdl.handle.net/10459.1/464100
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-099200-B-I00
Reproducció del document publica a: https://doi.org/10.1186/s13195-023-01278-7
Alzheimer’s Research & Therapy, 2023, vol. 15, Article number 134
dc.rights.none.fl_str_mv cc-by (c) Authors, 2023
Attribution 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
rights_invalid_str_mv cc-by (c) Authors, 2023
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BMC
publisher.none.fl_str_mv BMC
dc.source.none.fl_str_mv reponame:Repositori Obert UdL
instname:Universitat de Lleida (UdL)
instname_str Universitat de Lleida (UdL)
reponame_str Repositori Obert UdL
collection Repositori Obert UdL
repository.name.fl_str_mv
repository.mail.fl_str_mv
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