Neutrophil activation may trigger tau burden contributing to cognitive progression of chronic sleep disturbance in elderly individuals not living with dementia

BMC Medicine

Research Article

Wei Li¹  Jianhua Sheng¹  Shifu Xiao¹  Lin Sun¹  Jie Zhang² 

[1] Department of Psychiatry, Alzheimer’s Disease and Related Disorders Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, No. 600 South Wanping Road, Xuhui District, Shanghai, China;Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopedic Department of Tongji Hospital, School of Medicine, Tongji University, Shanghai, China;

关键词: Chronic sleep disturbance;    Cognitive progression;    Neutrophil;    Tau burden;    Alzheimer’s disease;   

DOI  :  10.1186/s12916-023-02910-x

 received in 2023-01-18, accepted in 2023-05-25,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundTo investigate the complex connection between chronic sleep disturbance (CSD) and cognitive progression.MethodsThe Alzheimer’s Disease Neuroimaging Initiative (ADNI) database was used to assign 784 non-dementia elderly into two groups: a normal sleep group (528 participants) and a CSD group (256 participants) via the Neuropsychiatric Inventory (NPI)-sleep subitem. Blood transcriptomics, blood neutrophil, cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD), and neutrophil-related inflammatory factors were measured. We also investigated gene set enrichment analysis (GSEA), Cox proportional hazards model for risk factors, and mediation and interaction effects between indicators. Cognitive progression is defined as the progression from cognitively normal to mild cognitive impairment (MCI)/dementia or from MCI to dementia.ResultsCSD could significantly affect cognitive function. The activated neutrophil pathways for cognitive progression in CSD were identified by transcriptomics GSEA, which was reflected by increased blood neutrophil level and its correlation with cognitive progression in CSD. High tau burden mediated the influence of neutrophils on cognitive function and exacerbated the CSD-related risk of left hippocampal atrophy. Elevated neutrophil-related inflammatory factors were observed in the cognitive progression of CSD and were associated with brain tau burden.ConclusionsActivated neutrophil pathway triggering tau pathology may underline the mechanism of cognitive progression in CSD.

【 授权许可】

CC BY   
© The Author(s) 2023

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