| Objective: With the development of aging population,neurodegenerative diseases are becoming more and more important in middle-aged and elderly people,which brings burden to patient caregivers and family society.As a response to microglial activation in the nervous system,cerebrospinal fluid(CSF)progranulin(PGRN)has been widely involved in various neurodegenerative diseases,such as frontotemporal dementia(FTD),Alzheimer ’s disease(AD),and Parkinson’ s disease.Sleep disorders are prominent in various clinical manifestations of neurodegenerative diseases.Chen D W et al(2018),Liguori C et al(2020)and Liu Z et al(2019)have demonstrated that some core proteins are abnormal in metabolism when sleep disorders occurred.We aim to explore the potential associations between self-reported sleep characteristics and CSF PGRN in cognitively intact older adults in order to replace core proteins with PGRN in the process of sleep disorders and discover a new theoretical support for sleep intervention in the treatment of neurodegenerative diseases.Methods: Chinese Alzheimer’s Biomarker and Lifesty IE(CABLE)study has an ongoing large-scale inpatient sample database based on Qingdao Municipal Hospital,Shandong Province,China.This study majorly focused on environmental or lifestyle risk factors and biomarkers of AD in Chinese Han population.Our study recruited 747participants(mean [standard deviation;SD] age,61.99 [10.52] years,329 [42.89%]females)who had normal cognition from the CABLE study with CSF PGRN measured and self-reported sleep characteristics using Pittsburgh sleep quality index(PSQI).The multiple linear regression and nonlinear regression adjusted for age,gender,education and apolipoprotein E-epsilon 4 gene(APOE4)status were used to assess the associations between sleep characteristics and PGRN.Interaction effects were explored between genders or APOE4 status and sleep characteristics on CSF PGRN level.Results: In primary analysis,the percentages of sleep characteristics in males such as long nocturnal sleep duration,short sleep latency,high sleep efficiency,and less to take sleep medicine but having snore are higher than those in females.The multiple linear regression showed that,in general,sleep disturbances indicated lower CSF PGRN(β =-0.0186,p = 0.0160).For detailed items in sleep disturbances,results between gender subgroups are inconsistent: lower CSF PGRN was found in males who woke up during sleep(β =-0.0121,p= 0.0062)and in females who had breathing difficulties(β =-0.0258,p = 0.0271).However,sleep efficiency was negatively associated with CSF PGRN(β =-0.0512,p = 0.0497).No significantly interaction effects between sleep characteristics and APOE4 status were found.Meanwhile,we didn’t find a nonlinear relationship between nocturnal sleep duration and CSF PGRN.Interpretation: Sleep problems may influence the metabolism of PGRN,thus attenuating the protective effects of PGRN on neurodegeneration diseases.Significance: Our first cross-sectional study of the association between PGRN and sleep in human shows that PGRN,a multifunctional growth factor widely studied in neurodegenerative diseases,also plays a role in human sleep.Healthy sleep is important to maintain PGRN homeostasis.This study not only reflects the possible etiological effects of sleep on neurodegeneration diseases,but also reflects that protein changes in neurodegenerative diseases may cause sleep problems.PGRN,as the protective role of the nervous system,can be maintained during healthy sleep.Once there is a problem in sleep and the level of PGRN decreases,its neuroprotective effect will be damaged. |
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