Sleep-related changes in astrocytic biomarkers are modulated by APOE ε4 genotype in cognitively unimpaired adults
Astrocytes are key regulators of sleep and neuroinflammatory responses. However, the relationship between objective sleep parameters and astrocytic fluid biomarkers in cognitively unimpaired individuals remains unclear. We examined how sleep architecture relates to astrocytic, neuroaxonal and Alzhei...
| Autores: | , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:322406 |
| Acceso en línea: | https://ddd.uab.cat/record/322406 https://dx.doi.org/urn:doi:10.1093/braincomms/fcaf437 |
| Access Level: | acceso abierto |
| Palabra clave: | Astrocytes Alzheimer's Disease-related proteins Polysomnography Apolipoprotein ε4 Cognitively unimpaired individual |
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| dc.title.none.fl_str_mv |
Sleep-related changes in astrocytic biomarkers are modulated by APOE ε4 genotype in cognitively unimpaired adults |
| title |
Sleep-related changes in astrocytic biomarkers are modulated by APOE ε4 genotype in cognitively unimpaired adults |
| spellingShingle |
Sleep-related changes in astrocytic biomarkers are modulated by APOE ε4 genotype in cognitively unimpaired adults Zhu, Nuole|||0000-0002-0015-9455 Astrocytes Alzheimer's Disease-related proteins Polysomnography Apolipoprotein ε4 Cognitively unimpaired individual |
| title_short |
Sleep-related changes in astrocytic biomarkers are modulated by APOE ε4 genotype in cognitively unimpaired adults |
| title_full |
Sleep-related changes in astrocytic biomarkers are modulated by APOE ε4 genotype in cognitively unimpaired adults |
| title_fullStr |
Sleep-related changes in astrocytic biomarkers are modulated by APOE ε4 genotype in cognitively unimpaired adults |
| title_full_unstemmed |
Sleep-related changes in astrocytic biomarkers are modulated by APOE ε4 genotype in cognitively unimpaired adults |
| title_sort |
Sleep-related changes in astrocytic biomarkers are modulated by APOE ε4 genotype in cognitively unimpaired adults |
| dc.creator.none.fl_str_mv |
Zhu, Nuole|||0000-0002-0015-9455 Altuna-Azkargorta, Miren|||0000-0001-9709-5314 Arranz Martínez, Javier|||0000-0003-0891-1215 Rodríguez-Baz, Íñigo|||0000-0003-3039-9115 Sánchez-Saudinós, María Belén|||0000-0003-1795-1833 Videla Toro, Laura|||0000-0002-9748-8465 Valldeneu, Silvia|||0000-0003-3497-886X Carreras-Vega, Mireia Romero, Sergio Fortea, Juan|||0000-0002-1340-638X Lleó, Alberto|||0000-0002-2568-5478 Giménez, Sandra|||0000-0001-8031-2319 Alcolea, Daniel|||0000-0002-3819-3245 |
| author |
Zhu, Nuole|||0000-0002-0015-9455 |
| author_facet |
Zhu, Nuole|||0000-0002-0015-9455 Altuna-Azkargorta, Miren|||0000-0001-9709-5314 Arranz Martínez, Javier|||0000-0003-0891-1215 Rodríguez-Baz, Íñigo|||0000-0003-3039-9115 Sánchez-Saudinós, María Belén|||0000-0003-1795-1833 Videla Toro, Laura|||0000-0002-9748-8465 Valldeneu, Silvia|||0000-0003-3497-886X Carreras-Vega, Mireia Romero, Sergio Fortea, Juan|||0000-0002-1340-638X Lleó, Alberto|||0000-0002-2568-5478 Giménez, Sandra|||0000-0001-8031-2319 Alcolea, Daniel|||0000-0002-3819-3245 |
| author_role |
author |
| author2 |
Altuna-Azkargorta, Miren|||0000-0001-9709-5314 Arranz Martínez, Javier|||0000-0003-0891-1215 Rodríguez-Baz, Íñigo|||0000-0003-3039-9115 Sánchez-Saudinós, María Belén|||0000-0003-1795-1833 Videla Toro, Laura|||0000-0002-9748-8465 Valldeneu, Silvia|||0000-0003-3497-886X Carreras-Vega, Mireia Romero, Sergio Fortea, Juan|||0000-0002-1340-638X Lleó, Alberto|||0000-0002-2568-5478 Giménez, Sandra|||0000-0001-8031-2319 Alcolea, Daniel|||0000-0002-3819-3245 |
| author2_role |
author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Astrocytes Alzheimer's Disease-related proteins Polysomnography Apolipoprotein ε4 Cognitively unimpaired individual |
| topic |
Astrocytes Alzheimer's Disease-related proteins Polysomnography Apolipoprotein ε4 Cognitively unimpaired individual |
| description |
Astrocytes are key regulators of sleep and neuroinflammatory responses. However, the relationship between objective sleep parameters and astrocytic fluid biomarkers in cognitively unimpaired individuals remains unclear. We examined how sleep architecture relates to astrocytic, neuroaxonal and Alzheimer's disease-related fluid biomarkers in cognitively unimpaired adults, and whether age, sex and APOE ε4 moderate these associations. This cross-sectional study included 51 cognitively unimpaired participants from the Sant Pau Initiative on Neurodegeneration cohort. One-night in-lab polysomnography was used to quantify sleep architecture, fragmentation, slow-wave activity, and respiratory parameters. CSF biomarkers included glial fibrillary acidic protein (GFAP), chitinase-like-3 protein 1 (YKL-40), Aβ42, Aβ40, pTau181, and tTau; plasma biomarkers included GFAP and neurofilament light chain (NfL). Associations were analyzed using Spearman correlations, multiple linear regression, and moderation models, adjusting for age, sex, body mass index, APOE ε4 status, and sleep apnea. Lighter and more fragmented sleep, characterized by longer N1 duration, increased wake after sleep onset, frequent stage transitions, and elevated cortical arousal, was associated with higher CSF YKL-40, Aβ40, pTau181 and tTau (rho = 0.32 to 0.62, all p<0.05). In contrast, deeper, more consolidated sleep, indicated by longer total time of sleep, greater N3 duration, and higher slow-wave activity, was associated with lower CSF GFAP and YKL-40 (rho = -0.35 to -0.44, all p<0.05). These associations remained significant in adjusted regression models. Plasma GFAP and NfL exhibited an inverse profile, with positive associations with deeper sleep (β: 0.16 to 0.18, p < 0.05) and negative associations with lighter sleep stages (β: -0.23 to -0.29, p < 0.01). REM sleep was also associated with astrocytic fluid biomarkers, with negative correlations for CSF and plasma GFAP (rho = -0.49 and rho = -0.28, respectively, all p<0.05), while in regression models REM duration remained a negative predictor of plasma GFAP (β = -0.23, p = 0.003) and a positive predictor of CSF YKL-40 (β = 0.12, p = 0.037). Notably, APOE ε4 consistently moderated associations between sleep and CSF YKL-40 and GFAP, while age and sex influenced plasma GFAP and CSF YKL-40, respectively (all p<0.05). In cognitively unimpaired adults, sleep architecture is differentially associated with central and peripheral biomarkers of astrocytic activation, neuroaxonal integrity and Alzheimer's disease-related proteins. These findings support the importance of considering sleep as a key factor in the early pathophysiology of neurodegenerative disease. |
| publishDate |
2025 |
| dc.date.none.fl_str_mv |
2 2025-01-01 2025 2025-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/322406 https://dx.doi.org/urn:doi:10.1093/braincomms/fcaf437 |
| url |
https://ddd.uab.cat/record/322406 https://dx.doi.org/urn:doi:10.1093/braincomms/fcaf437 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI21/00791 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI14/01126 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17/01019 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI20/01473 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI20/00836 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI13/01532 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI16/01825 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/00335 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI19/00882 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/00435 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI22/00611 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 INT19/00016 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 INT23/00048 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17/01896 |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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Universitat Autònoma de Barcelona |
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Dipòsit Digital de Documents de la UAB |
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1869408300130369537 |
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Sleep-related changes in astrocytic biomarkers are modulated by APOE ε4 genotype in cognitively unimpaired adultsZhu, Nuole|||0000-0002-0015-9455Altuna-Azkargorta, Miren|||0000-0001-9709-5314Arranz Martínez, Javier|||0000-0003-0891-1215Rodríguez-Baz, Íñigo|||0000-0003-3039-9115Sánchez-Saudinós, María Belén|||0000-0003-1795-1833Videla Toro, Laura|||0000-0002-9748-8465Valldeneu, Silvia|||0000-0003-3497-886XCarreras-Vega, MireiaRomero, SergioFortea, Juan|||0000-0002-1340-638XLleó, Alberto|||0000-0002-2568-5478Giménez, Sandra|||0000-0001-8031-2319Alcolea, Daniel|||0000-0002-3819-3245AstrocytesAlzheimer's Disease-related proteinsPolysomnographyApolipoprotein ε4Cognitively unimpaired individualAstrocytes are key regulators of sleep and neuroinflammatory responses. However, the relationship between objective sleep parameters and astrocytic fluid biomarkers in cognitively unimpaired individuals remains unclear. We examined how sleep architecture relates to astrocytic, neuroaxonal and Alzheimer's disease-related fluid biomarkers in cognitively unimpaired adults, and whether age, sex and APOE ε4 moderate these associations. This cross-sectional study included 51 cognitively unimpaired participants from the Sant Pau Initiative on Neurodegeneration cohort. One-night in-lab polysomnography was used to quantify sleep architecture, fragmentation, slow-wave activity, and respiratory parameters. CSF biomarkers included glial fibrillary acidic protein (GFAP), chitinase-like-3 protein 1 (YKL-40), Aβ42, Aβ40, pTau181, and tTau; plasma biomarkers included GFAP and neurofilament light chain (NfL). Associations were analyzed using Spearman correlations, multiple linear regression, and moderation models, adjusting for age, sex, body mass index, APOE ε4 status, and sleep apnea. Lighter and more fragmented sleep, characterized by longer N1 duration, increased wake after sleep onset, frequent stage transitions, and elevated cortical arousal, was associated with higher CSF YKL-40, Aβ40, pTau181 and tTau (rho = 0.32 to 0.62, all p<0.05). In contrast, deeper, more consolidated sleep, indicated by longer total time of sleep, greater N3 duration, and higher slow-wave activity, was associated with lower CSF GFAP and YKL-40 (rho = -0.35 to -0.44, all p<0.05). These associations remained significant in adjusted regression models. Plasma GFAP and NfL exhibited an inverse profile, with positive associations with deeper sleep (β: 0.16 to 0.18, p < 0.05) and negative associations with lighter sleep stages (β: -0.23 to -0.29, p < 0.01). REM sleep was also associated with astrocytic fluid biomarkers, with negative correlations for CSF and plasma GFAP (rho = -0.49 and rho = -0.28, respectively, all p<0.05), while in regression models REM duration remained a negative predictor of plasma GFAP (β = -0.23, p = 0.003) and a positive predictor of CSF YKL-40 (β = 0.12, p = 0.037). Notably, APOE ε4 consistently moderated associations between sleep and CSF YKL-40 and GFAP, while age and sex influenced plasma GFAP and CSF YKL-40, respectively (all p<0.05). In cognitively unimpaired adults, sleep architecture is differentially associated with central and peripheral biomarkers of astrocytic activation, neuroaxonal integrity and Alzheimer's disease-related proteins. These findings support the importance of considering sleep as a key factor in the early pathophysiology of neurodegenerative disease. 22025-01-0120252025-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/322406https://dx.doi.org/urn:doi:10.1093/braincomms/fcaf437reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI21/00791Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI14/01126Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17/01019Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI20/01473Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI20/00836Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI13/01532Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI16/01825Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/00335Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI19/00882Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/00435Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI22/00611Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 INT19/00016Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 INT23/00048Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17/01896open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3224062026-06-06T12:50:31Z |
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15,812455 |