ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Neurocognitive Aging and Behavior
Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1627774
Moderating effect of APOE ε4 on the association of sleep disturbance and amyloid-β pathology among cognitively normal older adults
Provisionally accepted
- 1Peking University Sixth Hospital, Beijing, China
- 2Xiamen Xianyue Hospital, Xianyue Hospital Affiliated with Xiamen Medical College，Fujian Psychiatric Center，Fujian Clinical Research Center for Mental Disorders, Xiamen, China
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Background: Sleep-wake rhythms are critical for the development of Alzheimer's disease (AD). However, the relationship of sleep disturbance, APOE ε4, and amyloid-β (Aβ) accumulation remains unclear. Thus, this study investigated the potential role of APOE ε4 allele in the association between sleep disturbance and brain Aβ burden among cognitively normal (CN) older adults. Methods: In this cross-sectional study, data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNl) Database. The sample consisted of CN individuals aged between 55 and 90 years with Aβ positron emission tomography scan, APOE genotype, and sleep assessment using the Neuropsychiatric Inventory.The study included 1,000 CN participants, including 134 individuals with sleep disturbances and 306 APOE ε4 carriers (APOE ε4+). After adjusting for sex, age, years of education, and marital status, sleep disturbance was not associated with a higher Aβ burden among participants. However, a significant interaction between sleep disturbance and APOE ε4 on regional standardized uptake value ratios was observed, such as in the left hippocampus. Subgroup analysis revealed that sleep disturbance could affect the AD-sensitive brain regions in the APOE ε4+ group. Furthermore, the subjective severity of sleep disturbance was linearly associated with a more significant Aβ brain burden in the APOE ε4+ group.: This study demonstrated that CN individuals with both APOE ε4+ status and sleep disturbance exhibited greater Aβ burden. Understanding the relationship between sleep and Aβ in CN older adults may inform sleep interventions that could reduce early Aβ accumulation and delay the onset of cognitive dysfunction associated with early AD.
Keywords: Alzheimer's disease, amyloid-β, APOE ε4, Moderating analysis, Sleep disturbance
Received: 13 May 2025; Accepted: 02 Sep 2025.
Copyright: © 2025 Feng, Que, Wang, Yuan and Shi. 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:
Kai Yuan, Peking University Sixth Hospital, Beijing, China
Le Shi, Peking University Sixth Hospital, Beijing, China
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