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中性粒细胞激活可能会引发 tau 负担，导致认知功能恶化，从而影响没有痴呆症的老年慢性睡眠障碍患者的认知进展。

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

机构信息

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.

出版信息

BMC Med. 2023 Jun 6;21(1):205. doi: 10.1186/s12916-023-02910-x.

DOI:10.1186/s12916-023-02910-x
PMID:37280592
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10243051/
Abstract

BACKGROUND

To investigate the complex connection between chronic sleep disturbance (CSD) and cognitive progression.

METHODS

The 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.

RESULTS

CSD 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.

CONCLUSIONS

Activated neutrophil pathway triggering tau pathology may underline the mechanism of cognitive progression in CSD.

摘要

背景

探讨慢性睡眠障碍（CSD）与认知进展之间的复杂关系。

方法

利用阿尔茨海默病神经影像学倡议（ADNI）数据库，通过神经精神问卷（NPI）-睡眠子项，将 784 名非痴呆老年人分为正常睡眠组（528 名参与者）和 CSD 组（256 名参与者）。检测血液转录组学、血液中性粒细胞、阿尔茨海默病（AD）的脑脊液（CSF）生物标志物和中性粒细胞相关炎症因子。还进行了基因集富集分析（GSEA）、危险因素的 Cox 比例风险模型以及指标之间的中介和交互作用分析。认知进展定义为从认知正常到轻度认知障碍（MCI）/痴呆或从 MCI 到痴呆的进展。

结果

CSD 可显著影响认知功能。通过转录组学 GSEA 确定了 CSD 中与认知进展相关的激活中性粒细胞途径，这反映在血液中性粒细胞水平升高及其与 CSD 中认知进展的相关性上。高 tau 负荷介导了中性粒细胞对认知功能的影响，并加重了 CSD 相关的左海马萎缩风险。CSD 认知进展中观察到升高的中性粒细胞相关炎症因子与脑 tau 负荷相关。

结论

激活的中性粒细胞途径触发 tau 病理学可能是 CSD 中认知进展的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/10243051/d7f7a3856a0e/12916_2023_2910_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/10243051/7975f10f2899/12916_2023_2910_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/10243051/1439b087ac08/12916_2023_2910_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/10243051/d7f7a3856a0e/12916_2023_2910_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/10243051/7975f10f2899/12916_2023_2910_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/10243051/565c1e471464/12916_2023_2910_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/10243051/ec0d9290935c/12916_2023_2910_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/10243051/1439b087ac08/12916_2023_2910_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/10243051/d7f7a3856a0e/12916_2023_2910_Fig5_HTML.jpg

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