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Profile of Pathogenic Proteins and MicroRNAs in Plasma-derived Extracellular Vesicles in Alzheimer's Disease: A Pilot Study.
Neuroscience ( IF 3.3 ) Pub Date : 2020-03-03 , DOI: 10.1016/j.neuroscience.2020.02.044
Fang Li 1 , Xin-Yu Xie 1 , Xia-Fei Sui 1 , Peng Wang 1 , Zhu Chen 1 , Jin-Biao Zhang 2
Affiliation  

Protein and miRNA enrichment within extracellular vesicles (EVs) isolated from patients with Alzheimer’s disease (AD) has been shown to have putative diagnostic value. However, whether a combination of both will be more advantageous is unknown. EVs were enriched from serum samples obtained from patients with sporadic AD (n=13), mild cognitive impairment (MCI) (n=10), vascular dementia (VaD) (n=10), and healthy controls (HC) (n=10). Expression of protein levels of Aβ1-42, total tau, P-T181-tau, and P-S396-tau and 18 microRNAs (miRNAs) in the EVs was performed by ELISA and qRT-PCR, respectively. Results were validated in an independent cohort of 18 subjects each by qRT-PCR assays. EV protein expression of Aβ1-42, total-tau, P-T181-tau and P-S396-tau, were significantly different among AD, MCI and VaD. Hsa-miR-1306-5p, hsa-miR-342-3p, and hsa-15b-3p were all significantly downregulated in patients with AD compared to HC (P<0.05), only hsa-miR-1306-5p expression was differentially expressed between AD, MCI, and VaD samples. Similarly, whereas all 14 miRNAs were significantly upregulated in patients with AD compared to HC, only hsa-miR-93-5p, hsa-miR-424-5p, and hsa-miR-3065-5p were differentially expressed when AD samples were compared to MCI and VaD samples. Even though the sample size was small, the results of the current pilot study indicates that hsa-miR-1306-5p, hsa-miR-93-5p, hsa-miR-424-5p, and hsa-miR-3065-5p, and expression of P-S396-tau in extracellular vesicles might provide a combinatorial protein and miRNA signature to differentiate between HC, patients with MCI or VaD from patient with sporadic AD.



中文翻译:

阿尔茨海默氏病血浆来源的细胞外囊泡中致病蛋白和MicroRNA的概况:一项先导研究。

从阿尔茨海默氏病(AD)患者中分离出的细胞外囊泡(EV)中的蛋白质和miRNA富集已被证明具有诊断价值。然而,尚不清楚两者的组合是否会更有利。从散发性AD(n = 13),轻度认知障碍(MCI)(n = 10),血管性痴呆(VaD)(n = 10)和健康对照(HC)(n = 10)。分别通过ELISA和qRT-PCR进行电动汽车中Aβ1-42,总tau,P-T181-tau和P-S396-tau和18个microRNA(miRNA)的蛋白水平表达。通过qRT-PCR分析在18名受试者的独立队列中验证了结果。AD,MCI和VaD之间Aβ1-42,总tau,P-T181-tau和P-S396-tau的EV蛋白表达差异显着。Hsa-miR-1306-5p,hsa-miR-342-3p,与HC相比,AD患者的hsa-15b-3p和hsa-15b-3p均显着下调(P <0.05),AD,MCI和VaD样品之间只有hsa-miR-1306-5p表达差异。同样,与HC相比,AD患者中所有14种miRNA均显着上调,但在比较AD样本时,只有hsa-miR-93-5p,hsa-miR-424-5p和hsa-miR-3065-5p差异表达。到MCI和VaD样品。尽管样本量很小,但当前的初步研究结果表明,hsa-miR-1306-5p,hsa-miR-93-5p,hsa-miR-424-5p和hsa-miR-3065-5p, P-S396-tau在细胞外小泡中的表达可能提供组合蛋白和miRNA信号,以区分HC,MCI或VaD患者与散发性AD患者。

更新日期:2020-03-03
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