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| Pàgina inicial > Articles > Articles publicats > Sleep-related changes in astrocytic biomarkers are modulated by APOE ε4 genotype in cognitively unimpaired adults |
(Institut de Recerca Sant Pau) (Fundación CITA-Alzhéimer Fundazioa (San Sebastián, País Basc)) (Institut de Recerca Sant Pau) (Institut de Recerca Sant Pau) (Institut de Recerca Sant Pau) (Institut de Recerca Sant Pau) (Institut de Recerca Sant Pau) (Universitat Autònoma de Barcelona. Departament de Medicina) (Institut de Recerca Sant Pau) (Institut de Recerca Sant Pau)
| Data: | 2025 |
| Resum: | 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. |
| Ajuts: | Instituto de Salud Carlos III PI21/00791 Ministerio de Economía y Competitividad PI14/01126 Instituto de Salud Carlos III PI17/01019 Instituto de Salud Carlos III PI20/01473 Instituto de Salud Carlos III PI20/00836 Ministerio de Economía y Competitividad PI13/01532 Ministerio de Economía y Competitividad PI16/01825 Instituto de Salud Carlos III PI18/00335 Instituto de Salud Carlos III PI19/00882 Instituto de Salud Carlos III PI18/00435 Instituto de Salud Carlos III PI22/00611 Instituto de Salud Carlos III INT19/00016 Instituto de Salud Carlos III INT23/00048 Instituto de Salud Carlos III PI17/01896 |
| Drets: | Aquest 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.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | Astrocytes ; Alzheimer's Disease-related proteins ; Polysomnography ; Apolipoprotein ε4 ; Cognitively unimpaired individual |
| Publicat a: | Brain Communications, november 2025, ISSN 2632-1297 |
