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. Overall design: Six nine-month old female SAMP8 mice were fed with vehicle diet and with CAD031 (200ppm). Diet treatment lasted for four months until mice reached thirteen months of age. Mice were then sacrificed and RNA extracted from the brain hippocampus. Five eight-month old male SAMP8 mice were used as the baseline control group (included in previous GEO accession GSE101112). For the in vitro experiments, Primary cortical neurons were prepared from day seventeen rat embryos and allowed to differentiate in culture. At seven days in vitro, neurons were treated with 1µM of the compound for 24h, and RNA purified.