Neurodegenerative diseases (NDs) are age-dependent; among them, Alzheimer's disease (AD) and Parkinson's disease (PD) are the most frequent. Similarly, cerebrovascular damage can induce the development of vascular-related disorders that share common features with AD and PD, respectively, named vascular dementia (VD) and vascular parkinsonism (VP). To date, ND diagnosis is mainly clinical; therefore, since these disorders show similar symptoms, their correct discrimination may be difficult. We detected 23 ND-associated microRNAs (miRNAs) by literature mining and investigated their serum expression in a cohort of 139 patients including AD, PD, VD, and VP patients and healthy controls. TaqMan RT-PCR data showed that miR-23a upregulation was associated with an ongoing neurodegenerative process, similar to miR-22* and miR-29a, while let-7d, miR-15b, miR-24, miR-142-3p, miR-181c, and miR-222 showed an altered expression in Parkinson-like phenotypes, as well as miR-34b, miR-125b, and miR-130b in Alzheimer-like disorders. By computing logistic regression models and ROC curves, we identified signatures of neuro-miRNAs specific for each disease, showing good diagnostic performance. Interestingly, we found that miR-23a, miR-29a, miR-34b, and miR-125b exhibited a different distribution between exosomes and vesicle-free serum, suggesting a heterogeneity of secretion for these miRNAs. Our results suggest that miRNA signatures could discriminate in a non-invasive manner neurodegenerative disorders, thus improving clinical diagnoses.

中文翻译：

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血清miRNA的特异性标志物可作为区分临床上类似的神经退行性疾病和血管相关疾病的潜在生物标记。

神经退行性疾病（NDs）依赖年龄。其中，阿尔茨海默氏病（AD）和帕金森氏病（PD）最常见。同样，脑血管损伤可诱发与血管性痴呆（VD）和血管性帕金森病（VP）分别与AD和PD具有共同特征的血管相关疾病的发展。迄今为止，ND诊断主要是临床性的。因此，由于这些疾病表现出相似的症状，因此难以正确区分。我们通过文献挖掘检测了23种与ND相关的microRNA（miRNA），并在139名包括AD，PD，VD和VP患者以及健康对照组的患者中研究了它们的血清表达。TaqMan RT-PCR数据显示，miR-23a的上调与正在进行的神经变性过程有关，类似于miR-22 *和miR-29a，而let-7d miR-15b，miR-24，miR-142-3p，miR-181c和miR-222在帕金森氏样表型以及miR-34b，miR-125b和miR-130b在阿尔茨海默氏症中表现出改变的表达。像疾病。通过计算逻辑回归模型和ROC曲线，我们确定了每种疾病特有的神经miRNA的特征，显示出良好的诊断性能。有趣的是，我们发现miR-23a，miR-29a，miR-34b和miR-125b在外泌体和无囊泡的血清之间表现出不同的分布，提示这些miRNA分泌的异质性。我们的结果表明，miRNA标记可以非侵入性方式区分神经退行性疾病，从而改善临床诊断。和miR-130b用于类似阿尔茨海默氏症的疾病。通过计算逻辑回归模型和ROC曲线，我们确定了每种疾病特有的神经miRNA的特征，显示出良好的诊断性能。有趣的是，我们发现miR-23a，miR-29a，miR-34b和miR-125b在外泌体和无囊泡的血清之间表现出不同的分布，提示这些miRNA分泌的异质性。我们的结果表明，miRNA标记可以非侵入性方式区分神经退行性疾病，从而改善临床诊断。和miR-130b用于类似阿尔茨海默氏症的疾病。通过计算逻辑回归模型和ROC曲线，我们确定了每种疾病特有的神经miRNA的特征，显示出良好的诊断性能。有趣的是，我们发现miR-23a，miR-29a，miR-34b和miR-125b在外泌体和无囊泡的血清之间表现出不同的分布，提示这些miRNA分泌的异质性。我们的结果表明，miRNA标记可以非侵入性方式区分神经退行性疾病，从而改善临床诊断。miR-125b和miR-125b在外泌体和无囊泡的血清之间表现出不同的分布，表明这些miRNA分泌的异质性。我们的结果表明，miRNA标记可以非侵入性方式区分神经退行性疾病，从而改善临床诊断。miR-125b和miR-125b在外泌体和无囊泡的血清之间表现出不同的分布，表明这些miRNA分泌的异质性。我们的结果表明，miRNA标记可以非侵入性方式区分神经退行性疾病，从而改善临床诊断。