血液RNA转录物显示阿尔茨海默病的炎症和脂质代谢以及轻度认知障碍的线粒体功能的变化。

IF 2.8 Q2 NEUROSCIENCES
Journal of Alzheimer's disease reports Pub Date : 2024-12-23 eCollection Date: 2024-01-01 DOI:10.1177/25424823241307878
Jun-Ichi Iga, Yuta Yoshino, Tomoki Ozaki, Ayumi Tachibana, Hiroshi Kumon, Yu Funahashi, Hiroaki Mori, Mariko Ueno, Yuki Ozaki, Kiyohiro Yamazaki, Shinichiro Ochi, Masakatsu Yamashita, Shu-Ichi Ueno
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引用次数: 0

摘要

背景:外周免疫异常在阿尔茨海默病(AD)的发病机制中有报道。目的:在本研究中,对AD患者、AD所致轻度认知障碍(MCI)患者和健康对照者进行血液转录组分析,以阐明免疫相关的病理生理学。方法:样本包括63名来自中山镇老年人完整枚举研究(Nakayama研究)的参与者,年龄超过65岁,诊断为(1)健康对照(N = 21,平均年龄:83.8岁),(2)AD导致MCI (N = 20,平均年龄:82.6岁),或(3)AD患者(N = 21,平均年龄:84.2岁)。每位参与者都接受了血液检查、核磁共振成像以及生活方式和认知功能问卷调查。通过转录组分析,通过基因本体分析、途径富集分析、匠心途径分析评估三组血中差异基因表达,并进行实时荧光定量PCR。结果:在AD中,中性粒细胞胞外陷阱信号增加,脂质代谢(FXR/RXR激活,三酰甘油降解)减少,而MCI通过减少中性粒细胞胞外陷阱信号和线粒体功能(如sirtuin途径上调和氧化应激下调)表现出保护反应。结论:基于这些发现,并与其他已发表的研究一致,免疫细胞似乎在AD的发病机制中起重要作用,血液中的转录组可以作为一种生物标志物,通过监测MCI和AD的免疫来诊断。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Blood RNA transcripts show changes in inflammation and lipid metabolism in Alzheimer's disease and mitochondrial function in mild cognitive impairment.

Background: Abnormal immunity in the periphery has been reported in the pathogenesis of Alzheimer's disease (AD).

Objective: In this study, blood transcriptome analyses of patients with AD, those with mild cognitive impairment (MCI) due to AD, and heathy controls were performed to elucidate immune-related pathophysiology.

Methods: The sample included 63 participants from a complete enumeration study of elderly people in Nakayama town (the Nakayama Study), who were over 65 years of age, diagnosed as (1) healthy controls (N = 21, mean age: 83.8 years), (2) having MCI due to AD (N = 20, mean age: 82.6 years), or (3) having AD (N = 21, mean age: 84.2 years). Every participant underwent blood tests, magnetic resonance imaging, and questionnaires about lifestyle and cognitive function. With transcriptome analysis, differential gene expressions in the blood of the three groups were evaluated by gene ontology, pathway enrichment, and ingenuity pathway analyses, and quantitative real-time PCR was performed.

Results: Neutrophil extracellular trap signaling was increased, and lipid metabolism (FXR/RXR activation, triacylglycerol degradation) was decreased in AD, whereas MCI showed protective responses via decreased neutrophil extracellular trap signaling and mitochondrial functions such as upregulation of the sirtuin pathway and downregulation of oxidative stress.

Conclusions: Based on these findings and consistent with other published studies, immune cells appear to have important roles in the pathogenesis of AD, and the transcriptome in blood may be useful as a biomarker for diagnosis via monitoring immunity in MCI and AD.

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