ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1552535
This article is part of the Research TopicSleep disturbances in Parkinson's disease and dementiaView all 3 articles
An investigation on Alzheimer's disease with obstructive sleep apnea: alterations of cognitive function, roles of cyclin-dependent kinase 5 and changes of brain structure
Provisionally accepted
Dongmei Luo
Tenghong Lian
Ning WeiPeng Guo
Mingyue He
Yanan Zhang
Yue Huang
Gaifen LiuJinghui LiJing QiHuiying GuanWenjing ZhangWeijia ZhangZijing ZhengHao Yue
Zhan LiuFan ZhangYao Meng
Wei Zhang*- Department of Neurology, Beijing Tiantan Hospital Capital Medical University, Beijing, China
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Aims: To investigate cognition, roles of cyclin-dependent kinase 5 (CDK5), and changes of brain structure in Alzheimer's disease with obstructive sleep apnea (AD-OSA). Methods: Total 94 AD-OSA patients were divided into 49 cases of AD with mild OSA (AD-OSA-M) and 45 cases of AD with moderate and severe OSA (AD-OSA-MS). Demographic characteristics, cognitive function, the levels of AD neuropathological proteins, CDK5 and synaptic proteins in cerebrospinal fluid (CSF), and brain volume by magnetic resonance imaging were compared between the two groups. The correlations between OSA and the above variables were analyzed. Results: Compared with AD-OSA-M group, AD-OSA-MS group had a higher body mass index, lower scores of AVLT N7 and SCWT-C, longer SCWT-C time, higher levels of phosphorylated tau (P-tau) 396 and synaptophysin, lower CDK5 level, and smaller volumes of brain gray and white matters in parts of frontal, parietal, temporal and occipital lobes. In AD-OSA patients, the decreased CDK5 level was correlated with the elevated levels of P-tau (S396) and synaptophysin in CSF. In AD-OSA-MS group, brain atrophy associated with OSA exacerbation was correlated with memory and executive function impairments. The P values of above results were < 0.05. Conclusion: In AD-OSA, OSA exacerbation is associated with memory impairment and executive dysfunction, P-tau 396 elevation and CDK5 decline in CSF (potential upregulation in brain), synaptic disruption, and brain atrophy. Additionally, CDK5 may represent a potential therapeutic target for the individuals with comorbid AD and OSA.
Keywords: Alzheimer's disease, obstructive sleep apnea, Cyclin-Dependent Kinase 5, Tau phosphorylation, synaptic dysfunction, brain structure
Received: 28 Dec 2024; Accepted: 21 Oct 2025.
Copyright: © 2025 Luo, Lian, Wei, Guo, He, Zhang, Huang, Liu, Li, Qi, Guan, Zhang, Zhang, Zheng, Yue, Liu, Zhang, Meng and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wei Zhang, ttyyzw@163.com
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