microRNA-132/212 deficiency enhances Ab production and senile plaque deposition in Alzheimer’s disease triple transgenic mice. Mus musculus

The abnormal regulation of amyloid-b (Ab) metabolism (e.g., production, cleavage, clearance) plays a central role in Alzheimer’s disease (AD). Among endogenous factors believed to participate in AD progression are the small regulatory non-coding microRNAs (miRs). In particular, the miR-132/212 cluster is severely reduced in the AD brain. In previous studies we have shown that miR-132/212 deficiency in mice leads to impaired memory and enhanced Tau pathology as seen in AD patients. Here we demonstrate that the genetic deletion of miR-132/212 promotes Ab deposition and amyloid (senile) plaque formation in triple transgenic AD (3xTg-AD) mice. Using RNA-Seq and bioinformatics, we identified genes of the miR-132/212 network with documented roles in the regulation of Ab metabolism, including Tau, Mapk, and Sirt1. Overall design: We used RNA-Seq to analyse the hippocampus of 3xTg-AD mice lacking the miR-132/212 cluster as well as Neuro2a cells overexpressing miR-132 mimics.