Title:Developmental Expression and Dysregulation of miR-146a and miR-155 in Down's Syndrome and Mouse Models of Down's Syndrome and Alzheimer's Disease
Volume: 14
Issue: 12
Author(s): A. Arena, A. M. Iyer, I. Milenkovic, G. G. Kovacs, I. Ferrer, M. Perluigi and E. Aronica*
Affiliation:
- Department of (Neuro) Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam,Netherlands
Keywords:
Hippocampus, development, Down's syndrome, Alzheimer's disease, Ts65Dn- APP/PS1, microRNAs.
Abstract: Background: miR-146a and miR-155 are key regulators of the innate immune response. We
hypothesized that an inflammation-mediated dysregulation of these miRNAs may occur in patients with
Down syndrome (DS) and Alzheimer's disease (AD).
Methods: The miRNA expression patterns were investigated by in situ hybridization in developing hippocampus
from controls, patients with DS and in adults with AD pathology (DS and sporadic AD;
sAD). Quantitative real-time PCR was employed to evaluate the miRNA levels in the hippocampus of
sAD and in mouse models of DS and AD. Both miRNAs were expressed in prenatal human hippocampus.
In DS we detected increased miR-146a expression in reactive astrocytes. Increased expression of
miR-146a was found in the hippocampus of sAD and negatively correlated with its target IRAK-1.
APP/PS1 mice showed a significant increase in the expression of both miRNAs at 11-13 months of age
as compared to WT and mice at 3 months. A negative correlation between miR-146a levels and its target
TRAF6 was observed in both Ts65Dn and APP/PS1 mice.
Conclusion: These findings suggest a possible involvement of miR-146a and miR-155 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.
