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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\u2019s disease-related fluid biomarkers in cognitively unimpaired adults and whether age, sex and APOE \u03b54 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), A\u03b242, A\u03b240, 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 \u03b54 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, A\u03b240, pTau181 and tTau (\u03c1 = 0.32\u20130.62, all P &amp;lt; 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 (\u03c1 = \u22120.35 to \u22120.44, all P &amp;lt; 0.05). These associations remained significant in adjusted regression models. Plasma GFAP and NfL exhibited an inverse profile, with positive associations with deeper sleep (\u03b2: 0.16\u20130.18, P &amp;lt; 0.05) and negative associations with lighter sleep stages (\u03b2: \u22120.23 to \u22120.29, P &amp;lt; 0.01). Rapid eye movement (REM) sleep was also associated with astrocytic fluid biomarkers, with negative correlations for CSF and plasma GFAP (\u03c1 = \u22120.49 and \u03c1 = \u22120.28, respectively, all P &amp;lt; 0.05), while in regression models, REM duration remained a negative predictor of plasma GFAP (\u03b2 = \u22120.23, P = 0.003) and a positive predictor of CSF YKL-40 (\u03b2 = 0.12, P = 0.037). Notably, APOE \u03b54 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 &amp;lt; 0.05). In cognitively unimpaired adults, sleep architecture is differentially associated with central and peripheral biomarkers of astrocytic activation, neuroaxonal integrity and Alzheimer\u2019s disease-related proteins. These findings support the importance of considering sleep as a key factor in the early pathophysiology of neurodegenerative disease.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf437","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T13:10:48Z","timestamp":1762434648000},"source":"Crossref","is-referenced-by-count":4,"title":["Sleep-related changes in astrocytic biomarkers are modulated by\n                    <i>APOE<\/i>\n                    \u03b54 genotype in cognitively unimpaired adults"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0015-9455","authenticated-orcid":false,"given":"Nuole","family":"Zhu","sequence":"first","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, IR SANT PAU, Hospital de la Santa Creu i Sant Pau , Barcelona 08025 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Neurodegenerativas (CIBERNED) , Madrid 28029 ,","place":["Spain"]},{"name":"Faculty of Medicine, Universitat Aut\u00f2noma de Barcelona , Barcelona 08193 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9709-5314","authenticated-orcid":false,"given":"Miren","family":"Altuna","sequence":"additional","affiliation":[{"name":"CITA-Alzheimer Foundation, Donostia-San Sebasti\u00e1n 20009 ,","place":["Spain"]},{"name":"Osakidetza, Organizaci\u00f3n Sanitaria Integrada (OSI) , Debabarrena 20850 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Arranz","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, IR SANT PAU, Hospital de la Santa Creu i Sant Pau , Barcelona 08025 ,","place":["Spain"]},{"name":"Faculty of Medicine, Universitat Aut\u00f2noma de Barcelona , Barcelona 08193 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00cd\u00f1igo","family":"Rodriguez-Baz","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, IR SANT PAU, Hospital de la Santa Creu i Sant Pau , Barcelona 08025 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Neurodegenerativas (CIBERNED) , Madrid 28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Bel\u00e9n","family":"Sanchez-Saudin\u00f3s","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, IR SANT PAU, Hospital de la Santa Creu i Sant Pau , Barcelona 08025 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Neurodegenerativas (CIBERNED) , Madrid 28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Videla","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, IR SANT PAU, Hospital de la Santa Creu i Sant Pau , Barcelona 08025 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Neurodegenerativas (CIBERNED) , Madrid 28029 ,","place":["Spain"]},{"name":"Barcelona Down Medical Center, Fundaci\u00f3 Catalana S\u00edndrome de Down , Barcelona 08041 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00edlvia","family":"Valldeneu","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, IR SANT PAU, Hospital de la Santa Creu i Sant Pau , Barcelona 08025 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Neurodegenerativas (CIBERNED) , Madrid 28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireia","family":"Carrera-Vega","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, IR SANT PAU, Hospital de la Santa Creu i Sant Pau , Barcelona 08025 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Romero","sequence":"additional","affiliation":[{"name":"Automatic Control Department (ESAII) and Institute for Research and Innovation in Health (IRIS), Universitat Polit\u00e8cnica de Catalunya-BarcelonaTech (UPC), BarcelonaTech (UPC) , Barcelona 08005 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1340-638X","authenticated-orcid":false,"given":"Juan","family":"Fortea","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, IR SANT PAU, Hospital de la Santa Creu i Sant Pau , Barcelona 08025 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Neurodegenerativas (CIBERNED) , Madrid 28029 ,","place":["Spain"]},{"name":"Barcelona Down Medical Center, Fundaci\u00f3 Catalana S\u00edndrome de Down , Barcelona 08041 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Lle\u00f3","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, IR SANT PAU, Hospital de la Santa Creu i Sant Pau , Barcelona 08025 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Neurodegenerativas (CIBERNED) , Madrid 28029 ,","place":["Spain"]},{"name":"Faculty of Medicine, Universitat Aut\u00f2noma de Barcelona , Barcelona 08193 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8031-2319","authenticated-orcid":false,"given":"Sandra","family":"Gim\u00e9nez","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, IR SANT PAU, Hospital de la Santa Creu i Sant Pau , Barcelona 08025 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Neurodegenerativas (CIBERNED) , Madrid 28029 ,","place":["Spain"]},{"name":"Multidisciplinary Sleep Unit, Respiratory Department, IR SANT PAU, Hospital de la Santa Creu i Sant Pau , Barcelona 08025 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3819-3245","authenticated-orcid":false,"given":"Daniel","family":"Alcolea","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, IR SANT PAU, Hospital de la Santa Creu i Sant Pau , Barcelona 08025 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Neurodegenerativas (CIBERNED) , Madrid 28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"issue":"1","key":"2025112901524021100_fcaf437-B1","doi-asserted-by":"crossref","DOI":"10.1093\/sleep\/zsw032","article-title":"Sleep, cognitive impairment, and Alzheimer\u2019s disease: A systematic review and meta-analysis","volume":"40","author":"Bubu","year":"2017","journal-title":"Sleep"},{"issue":"7_supplement_1","key":"2025112901524021100_fcaf437-B2","doi-asserted-by":"crossref","first-page":"3344","DOI":"10.1212\/WNL.0000000000205075","article-title":"The role of neuroinflammation in Alzheimer\u2019s disease: A systematic literature review 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