Department for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases, Göttingen, Germany.
Department for Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.
EMBO Mol Med. 2021 Nov 8;13(11):e13659. doi: 10.15252/emmm.202013659. Epub 2021 Oct 11.
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.
虽然有些人在衰老过程中没有出现病理性记忆障碍，但另一些人则会患上与年龄相关的认知疾病。由于这些患者的认知功能变化是随着时间的推移而缓慢发展的，因此他们通常在分子病理学的晚期才被诊断出来，而此时已经错过了治疗的时机。因此，非常需要找到一种廉价且微创的方法，以便进行筛查，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，我们采用了一种综合方法，结合了人类数据的分析和模型系统中的机制研究，以确定一个反映与神经内稳态相关的关键过程的循环 3 微 RNA 特征，并提供关于认知状态的信息。我们还提供了证据表明，该特征中的表达变化代表了衰老和患病大脑中多个失调的机制，是 RNA 治疗的一个合适靶点。
