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首页> 外文期刊>NPJ genomic medicine. >Brain microRNAs associated with late-life depressive symptoms are also associated with cognitive trajectory and dementia
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Brain microRNAs associated with late-life depressive symptoms are also associated with cognitive trajectory and dementia

机译：与晚生抑郁症状相关的脑微大血管也与认知轨迹和痴呆有关

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Late-life depression is associated with an increased risk for dementia but we have limited knowledge of the molecular mechanismsunderlying this association. Here we investigated whether brain microRNAs, important posttranscriptional regulators of geneexpression, contribute to this association. Late-life depressive symptoms were assessed annually in 300 participants of the ReligiousOrders Study and Rush Memory and Aging Project for a mean of 7 years. Participants underwent annual cognitive testing, clinicalassessment of cognitive status, and uniform neuropathologic examination after death. microRNAs were profiled from the prefrontalcortex using NanoString platform in the discovery cohort and small RNA sequencing in the replication cohort. A global microRNAassociation study of late-life depressive symptoms was performed using linear mixed model adjusting for the potentialconfounding factors. Four brain microRNAs were associated with late-life depressive symptoms at adjusted p 0.05: miR-484, miR26b-5p,miR-30d-5p, and miR-197-3p. Lower expression levels of these miRNAs were associated having greater depressivesymptoms. Furthermore, lower levels of miR-484 and miR-197-3p were associated with faster decline of cognition over time.Moreover, lower miR-484 level was associated with higher probability of having Alzheimer’s dementia. Importantly, the associationsbetween miR-484 and depressive symptoms and Alzheimer’s dementia, respectively, were replicated in an independent cohort.Lastly, the predicted targets of miR-484 were enriched in a brain protein co-expression module involving synaptic transmission andregulation of synaptic plasticity. This study identified four brain microRNAs associated with late-life depressive symptoms assessedlongitudinally. In addition, we found a molecular connection between late-life depression and dementia through miR-484.
机译：晚期抑郁症与痴呆症的风险增加有关，但我们对该协会的分子机制有限了解。在这里，我们调查了脑小罗车是否，重要的Geneexpression的重要监管机构，有助于这种协会。晚期抑郁症状每年在宗教者的300名参与者中进行评估，匆忙记忆和衰老项目的含义7年。参与者接受年度认知测试，临床评估认知状态，死亡后的神经病理学检查均匀。使用纳米复体平台在探测队列中的纳米复体平台和Repication Cohort中的小RNA测序中从预折叠平台中分析MicroRNA。利用线性混合模型调整潜在的Confoving因子进行了全球微小抑郁症状的全球微型抑郁症状。四个脑微小RNAS与调整后的P <0.05：miR-484，miR26b-5p，miR-30d-5p和miR-197-3p的后期抑郁症状有关。这些miRNA的较低表达水平伴有更大的抑制性关系。此外，较低水平的miR-484和miR-197-3p随时间的认知率越来越多地相关。发明，较低的miR-484水平与具有阿尔茨海默痴呆症的较高概率有关。重要的是，分别在一个独立的Cohort中分别复制miR-484和抑郁症状和阿尔茨海默痴呆症的关联.Lastly，MiR-484的预测靶标富集涉及突触速度和突触塑性的突触传递和调节的脑蛋白质共表达模块。本研究确定了与晚生抑郁症状相关的四种脑微大血淋，评估了。此外，我们发现通过MiR-484的晚期寿命抑郁和痴呆症之间的分子联系。

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