While some individuals age without pathological memory impairments, others develop age-associated cognitive diseases. Since changes in cognitive function develop slowly over time in these patients, they are often diagnosed at an advanced stage of molecular pathology, a time point when causative treatments fail. Thus, there is great need for the identification of inexpensive and minimal invasive approaches that could be used for screening with the aim to identify individuals at risk for cognitive decline that can then undergo further diagnostics and eventually stratified therapies. In this study, we use an integrative approach combining the analysis of human data and mechanistic studies in model systems to identify a circulating 3-microRNA signature that reflects key processes linked to neural homeostasis and inform about cognitive status. We furthermore provide evidence that expression changes in this signature represent multiple mechanisms deregulated in the aging and diseased brain and are a suitable target for RNA therapeutics.

中文翻译：

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与认知相关的 microRNA 特征，是对抗认知能力下降的目标

虽然有些人在衰老时没有病理性记忆障碍，但另一些人却患上了与年龄相关的认知疾病。由于这些患者的认知功能变化随着时间的推移而缓慢发展，因此他们通常是在分子病理学的晚期阶段（病因治疗失败时）才被诊断出来的。因此，非常需要找到廉价且微创的方法来进行筛查，目的是识别有认知能力下降风险的个体，然后进行进一步的诊断并最终进行分层治疗。在这项研究中，我们使用一种综合方法，将人类数据分析和模型系统中的机制研究相结合，以确定循环的 3-microRNA 特征，该特征反映了与神经稳态相关的关键过程并告知认知状态。我们还提供证据表明，这一特征的表达变化代表了衰老和患病大脑中多种机制失调，并且是 RNA 治疗的合适靶点。