Iga Jun-Ichi, Yoshino Yuta, Ozaki Tomoki, Tachibana Ayumi, Kumon Hiroshi, Funahashi Yu, Mori Hiroaki, Ueno Mariko, Ozaki Yuki, Yamazaki Kiyohiro, Ochi Shinichiro, Yamashita Masakatsu, Ueno Shu-Ichi
Department of Neuropsychiatry, Ehime University Graduate School of Medicine, Ehime, Japan.
Department of Immunology, Ehime University Graduate School of Medicine, Ehime, Japan.
J Alzheimers Dis Rep. 2024 Dec 23;8(1):1690-1703. doi: 10.1177/25424823241307878. eCollection 2024.
Abnormal immunity in the periphery has been reported in the pathogenesis of Alzheimer's disease (AD).
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.
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.
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.
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.
已有报道称外周免疫异常在阿尔茨海默病（AD）的发病机制中起作用。
在本研究中，对AD患者、因AD导致轻度认知障碍（MCI）的患者及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机制。
样本包括来自中山町老年人全面普查研究（中山研究）的63名参与者，他们年龄均超过65岁，被诊断为：（1）健康对照者（N = 21，平均年龄：83.8岁）；（2）因AD导致MCI者（N = 20，平均年龄：82.6岁）；或（3）AD患者（N = 21，平均年龄：84.2岁）。每位参与者均接受血液检查、磁共振成像检查以及关于生活方式和认知功能的问卷调查。通过转录组分析，利用基因本体论、通路富集分析和 Ingenuity 通路分析评估三组血液中的差异基因表达，并进行定量实时聚合酶链反应。
AD患者中中性粒细胞胞外诱捕信号增强，脂质代谢（法尼醇X受体/维甲酸X受体激活、三酰甘油降解）降低，而MCI患者通过降低中性粒细胞胞外诱捕信号和线粒体功能表现出保护性反应，如沉默调节蛋白通路上调和氧化应激下调。
基于这些发现并与其他已发表研究一致，免疫细胞似乎在AD发病机制中起重要作用，血液中的转录组可能作为一种生物标志物，通过监测MCI和AD中的免疫状态用于诊断。
