miR-212 and miR-132 Are Downregulated in Neurally Derived Plasma Exosomes of Alzheimer's Patients
miR-212 and miR-132 Are Downregulated in Neurally Derived Plasma Exosomes of Alzheimer's Patients
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DOI：
10.3389/fnins.2019.01208
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发表时间：
2019-11-26
影响因子：
4.3
通讯作者：
Walsh, Dominic M.
中科院分区：
文献类型：
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作者：
Cha, Diana J.;Mengel, David;Walsh, Dominic M.
最近发现，脑细胞释放细胞外囊泡（EV），可以从大脑传播到血液。这些发现增加了可以使用脑衍生的血液中的EV来监测大脑中发生的疾病过程的可能性。 Since the levels of certain micro-RNAs (miRNAs) have been reported to be altered in Alzheimer's disease (AD) brain, we sought to assess miRNA dysregulation in AD brain tissue and to determine if these changes were reflected in neural EVs isolated from blood of AD主题。为此，我们采用了高含有miRNA阵列来寻找来自AD（n = 5）的RNA库中的miRNA（n = 5），高病理控制（HPC）（n = 5）或认知完整的无病理控制（n = 5）。与对照组相比，AD的十二个miRNA被AD的> 1.5倍更改，与HPC相比，其中6个也改变了。分析来自11 AD，7个HPC和9个对照的脑提取物中的命中率显示出了这6个miRNA的折叠差异，其中3个显示出统计学上显着的组差异，其中1个具有强烈的群体差异趋势。此后，我们集中在四个miRNA上，这些miRNA显示了群体差异并测量了它们在从63名受试者中分离出的神经衍生的血液中的含量：16例早期痴呆症患者和CSF A Beta 42+ 42+ TAU型与AD一致的患者，16名轻度认知患者损伤（MCI）和AD CSF概况，以及31个具有正常CSF beta beta 42+ tau水平的认知完整控制。 ROC分析表明，在神经衍生的等离子体EV中，miR-132-3p的测量对诊断AD显示出良好的灵敏度和特异性，但没有有效地将AD-MCI的个体与对照组分开。此外，当我们测量相关miRNA的miRNA-miR-212水平时，我们发现与对照组相比，AD患者的神经电动汽车中这种miRNA也降低了。我们的结果表明，在神经电动汽车中，应进一步研究MiR-132和miR-212的测量，以作为AD的诊断辅助和潜在的TheTagnostic。
It was recently discovered that brain cells release extracellular vesicles (EV) which can pass from brain into blood. These findings raise the possibility that brain-derived EV's present in blood can be used to monitor disease processes occurring in the cerebrum. Since the levels of certain micro-RNAs (miRNAs) have been reported to be altered in Alzheimer's disease (AD) brain, we sought to assess miRNA dysregulation in AD brain tissue and to determine if these changes were reflected in neural EVs isolated from blood of subjects with AD. To this end, we employed high-content miRNA arrays to search for differences in miRNAs in RNA pools from brain tissue of AD (n = 5), high pathological control (HPC) (n = 5), or cognitively intact pathology-free controls (n = 5). Twelve miRNAs were altered by >1.5-fold in AD compared to controls, and six of these were also changed compared to HPCs. Analysis of hits in brain extracts from 11 AD, 7 HPCs and 9 controls revealed a similar fold difference in these six miRNAs, with three showing statistically significant group differences and one with a strong trend toward group differences. Thereafter, we focused on the four miRNAs that showed group differences and measured their content in neurally derived blood EVs isolated from 63 subjects: 16 patients with early stage dementia and a CSF A beta 42+ tau profile consistent with AD, 16 individuals with mild cognitive impairment (MCI) and an AD CSF profile, and 31 cognitively intact controls with normal CSF A beta 42+ tau levels. ROC analysis indicated that measurement of miR-132-3p in neurally-derived plasma EVs showed good sensitivity and specificity to diagnose AD, but did not effectively separate individuals with AD-MCI from controls. Moreover, when we measured the levels of a related miRNA, miR-212, we found that this miRNA was also decreased in neural EVs from AD patients compared to controls. Our results suggest that measurement of miR-132 and miR-212 in neural EVs should be further investigated as a diagnostic aid for AD and as a potential theragnostic.