Abstract：
Till date, there is an obvious obscurity of specific and early diagnostic biomarkers for Alzheimer\'s disease (AD). The promising diagnostic potential of serum miRNAs is increasingly emerging; however, rare miRNAs data originates from middle and low-income countries to provide proper validation in these highly affected populations. This study evaluated the diagnostic value of serum miR-34a, miR-29b and miR-181c in Egyptian AD patients.
Expression levels of serum miR-34a, miR-29b and miR-181c were determined using quantitative real time PCR in AD patients versus healthy controls. Amyloid Beta 42 (Aβ42), Phosphorylated Tau (p-Tau) and TNF-α levels were also detected as distinctive AD markers. We further explored the correlation between miRNAs levels and Mini mental state examination (MMSE) scores. Finally, we conducted logistic regression and ROC curve analyses to evaluate the diagnostic values of the measured parameters.
Sera miR-34a, miR-29b and miR-181c were significantly downregulated in AD patients and this decrease was associated with cognitive decline. AD patients manifested significant elevation of Aβ42, pTau and TNF-α levels. The measured miRNAs showed good AD diagnostic value solely and when used together (AUC = 0.77, 95 % C·I. 0.62-0.93 at p < 0.01). Interestingly, combining miRNAs panel with Aβ42, TNF-α and pTau levels remarkably increased the diagnostic power (AUC = 0.97, 95 % C·I. 0.94-1.00 at p < 0.001) achieving sensitivity 88.2 % and specificity 91.4 %.
This study spots for the first time the diagnostic potential of serum miR-34a, miR-29b and miR-181c as minimally invasive AD biomarker panel in Egyptian patients and highlights their contribution in AD pathogenesis.
Expression levels of serum miR-34a, miR-29b and miR-181c were determined using quantitative real time PCR in AD patients versus healthy controls. Amyloid Beta 42 (Aβ42), Phosphorylated Tau (p-Tau) and TNF-α levels were also detected as distinctive AD markers. We further explored the correlation between miRNAs levels and Mini mental state examination (MMSE) scores. Finally, we conducted logistic regression and ROC curve analyses to evaluate the diagnostic values of the measured parameters.
Sera miR-34a, miR-29b and miR-181c were significantly downregulated in AD patients and this decrease was associated with cognitive decline. AD patients manifested significant elevation of Aβ42, pTau and TNF-α levels. The measured miRNAs showed good AD diagnostic value solely and when used together (AUC = 0.77, 95 % C·I. 0.62-0.93 at p < 0.01). Interestingly, combining miRNAs panel with Aβ42, TNF-α and pTau levels remarkably increased the diagnostic power (AUC = 0.97, 95 % C·I. 0.94-1.00 at p < 0.001) achieving sensitivity 88.2 % and specificity 91.4 %.
This study spots for the first time the diagnostic potential of serum miR-34a, miR-29b and miR-181c as minimally invasive AD biomarker panel in Egyptian patients and highlights their contribution in AD pathogenesis.
摘要：
直到日期,阿尔茨海默病（AD）的特异性和早期诊断性生物标志物明显模糊。血清miRNAs的有希望的诊断潜力日益显现；然而，罕见的miRNAs数据来自中等和低收入国家，以在这些高度受影响的人群中提供适当的验证。本研究评估了血清miR-34a的诊断价值。miR-29b和miR-181c在埃及AD患者中的表达。
血清miR-34a的表达水平,使用定量实时PCR在AD患者与健康对照中测定miR-29b和miR-181c。淀粉样β42(Aβ42),磷酸化Tau（p-Tau）和TNF-α水平也被检测为独特的AD标记。我们进一步探索了miRNA水平与迷你精神状态检查（MMSE）评分之间的相关性。最后,我们进行了logistic回归和ROC曲线分析,以评估测量参数的诊断价值.
血清miR-34a,miR-29b和miR-181c在AD患者中显著下调，这种降低与认知功能下降相关。AD患者表现为Aβ42，pTau和TNF-α水平显着升高。单独和一起使用时，测得的miRNA显示出良好的AD诊断价值（AUC=0.77，95％C·I。0.62-0.93，p<0.01）。有趣的是,将miRNAs组与Aβ42，TNF-α和pTau水平相结合，可显着提高诊断能力（AUC=0.97，95％C·I。0.94-1.00，p<0.001），灵敏度为88.2%，特异性为91.4%。
这项研究首次发现了血清miR-34a的诊断潜力，miR-29b和miR-181c作为埃及患者的微创AD生物标志物组，并强调了它们在AD发病机理中的作用。
血清miR-34a的表达水平,使用定量实时PCR在AD患者与健康对照中测定miR-29b和miR-181c。淀粉样β42(Aβ42),磷酸化Tau（p-Tau）和TNF-α水平也被检测为独特的AD标记。我们进一步探索了miRNA水平与迷你精神状态检查（MMSE）评分之间的相关性。最后,我们进行了logistic回归和ROC曲线分析,以评估测量参数的诊断价值.
血清miR-34a,miR-29b和miR-181c在AD患者中显著下调，这种降低与认知功能下降相关。AD患者表现为Aβ42，pTau和TNF-α水平显着升高。单独和一起使用时，测得的miRNA显示出良好的AD诊断价值（AUC=0.77，95％C·I。0.62-0.93，p<0.01）。有趣的是,将miRNAs组与Aβ42，TNF-α和pTau水平相结合，可显着提高诊断能力（AUC=0.97，95％C·I。0.94-1.00，p<0.001），灵敏度为88.2%，特异性为91.4%。
这项研究首次发现了血清miR-34a的诊断潜力，miR-29b和miR-181c作为埃及患者的微创AD生物标志物组，并强调了它们在AD发病机理中的作用。
