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鉴定循环 miR-125b 作为 APP/PS1 转基因小鼠阿尔茨海默病的潜在生物标志物。

Identification of Circulating miR-125b as a Potential Biomarker of Alzheimer's Disease in APP/PS1 Transgenic Mouse.

机构信息

Department of Clinical Laboratory, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.

出版信息

J Alzheimers Dis. 2017;59(4):1449-1458. doi: 10.3233/JAD-170156.

Abstract

Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive decline in cognitive abilities of the affected individuals. Biological markers are essential to identify individuals at early stages of the disease for timely therapeutic intervention. Currently, pathological biomarkers are detected either through cerebrospinal fluid analysis or brain imaging, or postmortem, all of which are expensive, invasive, or time consuming. Recently, some studies have shown that circulating miR-125b, miR-181c, miR-9, miR-191-5p, miR-26b-3p, and miR-28-3p may be biomarkers of AD. However, those potential biomarkers are not validated in an AD mouse model. In the current study, we found that circulating miR-125b, miR-9, and miR-191-5p are downregulated, and miR-28-3p is upregulated in an APP/PS1 transgenic mouse model of AD. Furthermore, the correlation analysis shows a positive correlation between the expression of miR-125b and cognitive function of the APP/PS1 transgenic mouse. Moreover, we also determined that the level of serum miR-125b, miR-9, and miR-191-5p were reversed in EGCG-treated APP/PS1 transgenic mouse models. Finally, the expression of miR-125b was significantly downregulated in EGCG-treated SH-SY5Y cells.

摘要

阿尔茨海默病(AD)是最常见的痴呆症形式,其特征是受影响个体的认知能力逐渐下降。生物标志物对于在疾病的早期阶段识别个体以进行及时的治疗干预至关重要。目前,病理生物标志物要么通过脑脊液分析或脑成像,要么通过死后检测来检测,这些方法都既昂贵又具有侵入性,或者耗时较长。最近,一些研究表明,循环中的 miR-125b、miR-181c、miR-9、miR-191-5p、miR-26b-3p 和 miR-28-3p 可能是 AD 的生物标志物。然而,这些潜在的生物标志物尚未在 AD 小鼠模型中得到验证。在本研究中,我们发现循环中的 miR-125b、miR-9 和 miR-191-5p 在 AD 的 APP/PS1 转基因小鼠模型中下调,而 miR-28-3p 上调。此外,相关性分析显示 miR-125b 的表达与 APP/PS1 转基因小鼠的认知功能呈正相关。此外,我们还确定了 EGCG 处理的 APP/PS1 转基因小鼠模型中血清 miR-125b、miR-9 和 miR-191-5p 的水平得到了逆转。最后,miR-125b 在 EGCG 处理的 SH-SY5Y 细胞中的表达明显下调。

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