Sleep-related changes in astrocytic biomarkers are modulated by APOE e4 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...

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Autores: Zhu N, Altuna M, Arranz J, Rodriguez-Baz Í, Sanchez-Saudinós MB, Videla L, Valldeneu S, Carrera-Vega M, Romero S, Fortea J, Lleó A, Giménez S, Alcolea D
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p29508
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=29508
Access Level:acceso abierto
Palabra clave:Alzheimer’s disease-related proteins
apolipoprotein e4
astrocytes
cognitively unimpaired individual
polysomnography
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spelling Sleep-related changes in astrocytic biomarkers are modulated by APOE e4 genotype in cognitively unimpaired adults.Zhu NAltuna MArranz JRodriguez-Baz ÍSanchez-Saudinós MBVidela LValldeneu SCarrera-Vega MRomero SFortea JLleó AGiménez SAlcolea DAlzheimer’s disease-related proteinsapolipoprotein e4astrocytescognitively unimpaired individualpolysomnographyAstrocytes 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 e4 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), Aß42, Aß40, pTau181 and tTau; plasma biomarkers included GFAP and neurofilament light chain (NfL). Associations were analysed using Spearman correlations, multiple linear regression, and moderation models, adjusting for age, sex, body mass index, APOE e4 status and sleep apnoea. 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, Aß40, pTau181 and tTau (? = 0.32-0.62, 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 (? = -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 (ß: 0.16-0.18, P < 0.05) and negative associations with lighter sleep stages (ß: -0.23 to -0.29, P < 0.01). Rapid eye movement (REM) sleep was also associated with astrocytic fluid biomarkers, with negative correlations for CSF and plasma GFAP (? = -0.49 and ? = -0.28, respectively, all P < 0.05), while in regression models, REM duration remained a negative predictor of plasma GFAP (ß = -0.23, P = 0.003) and a positive predictor of CSF YKL-40 (ß = 0.12, P = 0.037). Notably, APOE e4 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.OXFORD UNIV PRESS2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=29508Brain CommunicationsISSN: 26321297reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p295082026-05-27T12:37:41Z
dc.title.none.fl_str_mv Sleep-related changes in astrocytic biomarkers are modulated by APOE e4 genotype in cognitively unimpaired adults.
title Sleep-related changes in astrocytic biomarkers are modulated by APOE e4 genotype in cognitively unimpaired adults.
spellingShingle Sleep-related changes in astrocytic biomarkers are modulated by APOE e4 genotype in cognitively unimpaired adults.
Zhu N
Alzheimer’s disease-related proteins
apolipoprotein e4
astrocytes
cognitively unimpaired individual
polysomnography
title_short Sleep-related changes in astrocytic biomarkers are modulated by APOE e4 genotype in cognitively unimpaired adults.
title_full Sleep-related changes in astrocytic biomarkers are modulated by APOE e4 genotype in cognitively unimpaired adults.
title_fullStr Sleep-related changes in astrocytic biomarkers are modulated by APOE e4 genotype in cognitively unimpaired adults.
title_full_unstemmed Sleep-related changes in astrocytic biomarkers are modulated by APOE e4 genotype in cognitively unimpaired adults.
title_sort Sleep-related changes in astrocytic biomarkers are modulated by APOE e4 genotype in cognitively unimpaired adults.
dc.creator.none.fl_str_mv Zhu N
Altuna M
Arranz J
Rodriguez-Baz Í
Sanchez-Saudinós MB
Videla L
Valldeneu S
Carrera-Vega M
Romero S
Fortea J
Lleó A
Giménez S
Alcolea D
author Zhu N
author_facet Zhu N
Altuna M
Arranz J
Rodriguez-Baz Í
Sanchez-Saudinós MB
Videla L
Valldeneu S
Carrera-Vega M
Romero S
Fortea J
Lleó A
Giménez S
Alcolea D
author_role author
author2 Altuna M
Arranz J
Rodriguez-Baz Í
Sanchez-Saudinós MB
Videla L
Valldeneu S
Carrera-Vega M
Romero S
Fortea J
Lleó A
Giménez S
Alcolea D
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alzheimer’s disease-related proteins
apolipoprotein e4
astrocytes
cognitively unimpaired individual
polysomnography
topic Alzheimer’s disease-related proteins
apolipoprotein e4
astrocytes
cognitively unimpaired individual
polysomnography
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 e4 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), Aß42, Aß40, pTau181 and tTau; plasma biomarkers included GFAP and neurofilament light chain (NfL). Associations were analysed using Spearman correlations, multiple linear regression, and moderation models, adjusting for age, sex, body mass index, APOE e4 status and sleep apnoea. 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, Aß40, pTau181 and tTau (? = 0.32-0.62, 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 (? = -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 (ß: 0.16-0.18, P < 0.05) and negative associations with lighter sleep stages (ß: -0.23 to -0.29, P < 0.01). Rapid eye movement (REM) sleep was also associated with astrocytic fluid biomarkers, with negative correlations for CSF and plasma GFAP (? = -0.49 and ? = -0.28, respectively, all P < 0.05), while in regression models, REM duration remained a negative predictor of plasma GFAP (ß = -0.23, P = 0.003) and a positive predictor of CSF YKL-40 (ß = 0.12, P = 0.037). Notably, APOE e4 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 2025
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://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=29508
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=29508
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv OXFORD UNIV PRESS
publisher.none.fl_str_mv OXFORD UNIV PRESS
dc.source.none.fl_str_mv Brain Communications
ISSN: 26321297
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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