Air pollution and Alzheimer disease phenotype deplete esterified pro-resolving lipid mediator reserves in the brain.

IF 6.3 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

JCI insight Pub Date : 2025-05-13 DOI:10.1172/jci.insight.175917

Ameer Y Taha, Qing Shen, Yurika Otoki, Nuanyi Liang, Kelley T Patten, Anthony E Valenzuela, Christopher D Wallis, Douglas J Rowland, Abhijit J Chaudhari, Keith J Bein, Anthony S Wexler, Lee-Way Jin, Brittany N Dugger, Danielle J Harvey, Pamela J Lein

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Abstract

Background: Traffic-related air pollution (TRAP) is a risk factor for Alzheimer disease (AD), where unresolved brain inflammation has been linked to deficits in the levels of free lipid mediators that enable the resolution of inflammation. It is unknown whether these deficits are due to reductions in esterified lipid pools, the main source of free bioactive pro-resolving lipids in the brain, and whether they are related AD pathophysiology.

Methods: This unknown was tested by measuring brain esterified lipid mediators and pathogenic markers of AD in TgF344-AD and wildtype (WT) male and female rats exposed to filtered air or TRAP for 14 months, and in human postmortem pre-frontal cortex of individuals with or without AD.

Results: Significant reductions in pro-resolving lipid mediators esterified to neutral lipids and/or phospholipids were seen in AD and TRAP-exposed female rats, where levels were associated with inflammation, synaptic loss and impaired glucose metabolism. Lower esterified pro-resolving lipid mediator concentrations were associated with older age in pre-frontal cortex of humans with AD.

Conclusion: Impaired resolution in AD is due to depletion of esterified pro-resolving lipid pools that supply the brain with free bioactive mediators involved in inflammation resolution. TRAP exposure alters the same esterified resolution pathways, reflecting convergent mechanisms underlying AD.

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空气污染和阿尔茨海默病表型消耗脑中酯化促溶解脂质介质储备。

背景：交通相关的空气污染（TRAP）是阿尔茨海默病（AD）的一个危险因素，其中未解决的脑炎症与能够解决炎症的游离脂质介质水平的缺陷有关。目前尚不清楚这些缺陷是否由于酯化脂质池（大脑中游离生物活性促分解脂质的主要来源）的减少，以及它们是否与阿尔茨海默病病理生理有关。方法：通过测量暴露于过滤空气或陷阱14个月的TgF344-AD和野生型（WT）雄性和雌性大鼠的脑酯化脂质介质和AD致病标志物，以及患有或不患有AD的人死后前额叶皮层，对这一未知进行了测试。结果：在AD和trap暴露的雌性大鼠中，被酯化成中性脂质和/或磷脂的促溶解脂质介质显著减少，其水平与炎症、突触丧失和糖代谢受损有关。较低的酯化促分解脂质介质浓度与阿尔茨海默病患者前额皮质的年龄有关。结论：AD的消退受损是由于为大脑提供参与炎症消退的游离生物活性介质的酯化促消退脂质池的耗尽。TRAP暴露改变了相同的酯化分解途径，反映了AD的趋同机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

JCI insight Medicine-General Medicine

CiteScore

13.70

自引率

1.20%

发文量

543

审稿时长

6 weeks

期刊介绍： JCI Insight is a Gold Open Access journal with a 2022 Impact Factor of 8.0. It publishes high-quality studies in various biomedical specialties, such as autoimmunity, gastroenterology, immunology, metabolism, nephrology, neuroscience, oncology, pulmonology, and vascular biology. The journal focuses on clinically relevant basic and translational research that contributes to the understanding of disease biology and treatment. JCI Insight is self-published by the American Society for Clinical Investigation (ASCI), a nonprofit honor organization of physician-scientists founded in 1908, and it helps fulfill the ASCI's mission to advance medical science through the publication of clinically relevant research reports.