Whole transcriptome analysis of brain hippocampal tissue from SAMP8 mice and rat primary neurons treated with the Alzheimer’s disease drug candidate CAD031

Alzheimer’s disease (AD) drug discovery has rarely been addressed in the context of aging even though sporadic AD accounts for 99% of the cases. Phenotypic screens based upon old age-associated brain toxicities were used to develop the potent AD drug candidate CAD031. The aim of this project was to investigate whether CAD031 prevented the progression of dementia in SAMP8 mice when administered at advanced stages of disease, and the possible mechanism of this prevention effect. These transcriptomic data are part of an integrative multi-omics approach that also investigated protein expression, metabolite levels as well as cognition. In addition, in order to further investigate the effect of the drugs in in vitro neuronal cultures, rat primary neurons were treated with the compound and the transcriptome sequenced.尽管散发性阿尔茨海默病（sporadic AD）占全部阿尔茨海默病病例的99%，但以衰老为研究背景的阿尔茨海默病药物研发却鲜有涉足。研究人员依托衰老相关脑毒性构建表型筛选模型，成功开发出强效阿尔茨海默病候选药物CAD031。本项目旨在探究：在疾病晚期给药时，CAD031是否能够延缓SAMP8小鼠的痴呆进程，并解析该防治作用的潜在分子机制。本次研究产生的转录组数据隶属于一项整合多组学研究，该研究同时涵盖了蛋白质表达、代谢物水平及认知功能的检测分析。此外，为进一步探究该化合物在体外神经元培养体系中的生物学效应，研究人员对大鼠原代神经元施加该化合物并开展转录组测序。