Abstract
As brain insults, sleep disorders could enhance microglial activation and aggravate neuroinflammation. Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) serves as a readout for TREM2-associated microglial responses. We aimed to study the association of sleep characteristics with CSF sTREM2 in cognitively normal (CN) older adults. Linear and non-linear regression analyses were conducted in 830 participants with measurements of sleep characteristics and CSF sTREM2, after adjusting for age, sex, education, the Chinese-Modified Mini-Mental State Examination (CM-MMSE) scores, and APOE4 status. These analyses were also performed in amyloid-negative (A −) and amyloid-positive (A +) individuals. Linear relationships between sleep characteristics and CSF sTREM2 were found. In all the participants, sleep efficiency score in Pittsburgh Sleep Quality Index (PSQI) (p = 0.037) showed a positive linear association with CSF sTREM2. In A + individuals, the grade of PSQI total score (p = 0.011) as well as subjective sleep quality score (p = 0.048) and sleep efficiency score (p < 0.001) in PSQI were positively associated with CSF sTREM2. Besides, several U-shaped relationships were revealed of sleep-time measures, such as insufficient or excessive nocturnal sleep duration, with CSF sTREM2 in A + individuals (the optimal model: bedtime 22:21 p.m., time to fall asleep 22:52 p.m., nocturnal sleep duration 7.36 h). In A − individuals, the above relationships were not found. Poor self-reported sleep characteristics and sleep indicators were associated with higher CSF sTREM2, suggesting that sleep might play an important role in the regulation of TREM2-associated microglial activity.
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Data Availability
The datasets used during the current study are available from the corresponding author on reasonable request.
Abbreviations
- sTREM2:
-
Soluble triggering receptor expressed on myeloid cells 2
- CSF:
-
Cerebrospinal fluid
- CN:
-
Cognitively normal
- MCI:
-
Mild cognitive impairment
- AD:
-
Alzheimer’s disease
- NIA–AA:
-
National Institute on Aging–Alzheimer’s Association
- CM-MMSE:
-
Chinese-Modified Mini-Mental State Examination
- MoCA:
-
Montreal Cognitive Assessment
- A − :
-
Amyloid-negative
- A + :
-
Amyloid-positive
- PSQI:
-
Pittsburgh Sleep Quality Index
- CNS:
-
Central nervous system
- TREM2:
-
Triggering receptor expressed on myeloid cells 2
- ADAM:
-
Disintegrin and metalloproteinase domain-containing protein
- CABLE:
-
Chinese Alzheimer’s Biomarker and Lifestyle
- RFLP:
-
Restriction fragment length polymorphism
- SD:
-
Standardized deviations
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Acknowledgements
We gratefully acknowledge the colleagues who have made contributions to build the CABLE cohort.
Funding
This study was supported by grants from the National Natural Science Foundation of China (91849126), the National Key R&D Program of China (2018YFC1314700), Shanghai Municipal Science and Technology Major Project (No. 2018SHZDZX01) and Zhangjiang Lab, Tianqiao and Chrissy Chen Institute, and the State Key Laboratory of Neurobiology and Frontiers Center for Brain Science of Ministry of Education, Fudan University.
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HYH, LZM, HH, LT, and JTY did the manuscript preparation and drafting. HYH, LZM, HH, YLB, XNS, YNO, YHM, and JTY did the clinical assessments and data acquisition. LT and JTY did the clinical diagnosis. HYH, LZM, and HH did the data analysis and interpretation. LT and JTY are responsible for the study conception and design. All authors have contributed to the manuscript, revising and editing critically for important intellectual content, given final approval of the version, and agreed to be accountable for all aspects of the work presented here.
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The design of CABLE was approved by the institutional review boards of Qingdao Municipal Hospital. According to the Declaration of Helsinki, written informed consent was obtained from all participants or their guardians.
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Hu, HY., Ma, LZ., Hu, H. et al. Associations of Sleep Characteristics with Cerebrospinal Fluid sTREM2 in Cognitively Normal Older Adults: the CABLE Study. Neurotox Res 39, 1372–1380 (2021). https://doi.org/10.1007/s12640-021-00383-5
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DOI: https://doi.org/10.1007/s12640-021-00383-5