A microRNA signature for early detection and RNA therapy in Alzheimer's disease (small RNA)

Since changes in cognitive function develop slowly over time, Alzheimer's disease patients are often diagnosed at an advanced stage of molecular pathology, a time point when causative treatments fail. Thus, there is great need for inexpensive and minimal invasive biomarker that could be used in screening approaches with the aim to identify individuals at risk, 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 model systems to identify a circulating 3-microRNA signature that reflect key processes linked to neural homeostasis and informs about cognitive decline. We furthermore provide evidence that expression changes of this signature represent relevant patho-mechanisms in the brain and are a suitable target for RNA therapeutics towards dementia. Longitudinal analysis of smallRNAseq data along aging in mice由于认知功能的变化随时间缓慢进展，阿尔茨海默病（Alzheimer's disease）患者往往在分子病理学的晚期阶段才被确诊，此时致病治疗已难以奏效。因此，亟需开发廉价且微创的生物标志物（biomarker），用于筛查潜在患病风险人群，以便对其开展进一步诊断并最终实施分层治疗。本研究采用整合研究策略，整合人类数据分析与模型系统分析，以鉴定出一种循环型3-微RNA（3-microRNA）特征谱，该特征谱可反映与神经内稳态（neural homeostasis）相关的关键生物学过程，并可提示认知功能衰退情况。此外，本研究还证实，该特征谱的表达变化可反映大脑内相关的病理机制，且可作为治疗痴呆症的RNA治疗剂（RNA therapeutics）的合适靶点。本研究同时包含小鼠衰老过程中小RNA测序（smallRNAseq）数据的纵向分析。