P 161 - Developmental expression and dysregulation of miR146a and miR155 in Down's syndrome and mouse models of Down's syndrome and Alzheimer's disease

Abstract

Increasing evidence supports the involvement of inflammation-related miRNAs in neural development and function under pathological conditions. We hypothesized that an dysregulation of miR146a and miR155, key regulators of the innate immune response, may occur in patients with Down syndrome (DS) and Alzheimer's disease (AD). The miRNA expression patterns were investigated in developing hippocampus from DS and in DS-AD adults. Quantitative RT-PCR was employed to evaluate the miRNA levels in the AD hippocampus at different stage of disease (sAD) and in DS (Ts65Dn) and AD (APP/PS1) mouse models. Both miRNAs were expressed in prenatal human hippocampus. In DS we detected increased miR146a expression in reactive astrocytes, which was also found in hippocampus of sAD and negatively correlated with its target IRAK1. APP/PS1 mice showed a significant expression increase of both miRNAs at 11–13 months of age as compared to wt and mice at 3 months. A negative correlation between miR146a levels and its target TRAF6 was observed in both mice models. These findings suggest a possible involvement of miR146a and miR155 in brain development and neurodegeneration. In particular, we provide evidence of a dysregulation of these two immunomodulatory miRNAs in AD with a potential therapeutical implication, deserving further investigation.