Alteration of the microRNA network during the progression of Alzheimer's disease
Article first published online: 9 SEP 2013
Copyright © 2013 EMBO Molecular Medicine
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
EMBO Molecular Medicine
Volume 5, Issue 10, pages 1613–1634, October 2013
How to Cite
Lau, P., Bossers, K., Janky, R., Salta, E., Frigerio, C. S., Barbash, S., Rothman, R., Sierksma, A. S. R., Thathiah, A., Greenberg, D., Papadopoulou, A. S., Achsel, T., Ayoubi, T., Soreq, H., Verhaagen, J., Swaab, D. F., Aerts, S. and De Strooper, B. (2013), Alteration of the microRNA network during the progression of Alzheimer's disease. EMBO Mol Med, 5: 1613–1634. doi: 10.1002/emmm.201201974
- Issue published online: 2 OCT 2013
- Article first published online: 9 SEP 2013
- Manuscript Accepted: 26 JUL 2013
- Manuscript Revised: 25 JUL 2013
- Manuscript Received: 3 SEP 2012
- Alzheimer's disease;
- prefrontal cortex;
An overview of miRNAs altered in Alzheimer's disease (AD) was established by profiling the hippocampus of a cohort of 41 late-onset AD (LOAD) patients and 23 controls, showing deregulation of 35 miRNAs. Profiling of miRNAs in the prefrontal cortex of a second independent cohort of 49 patients grouped by Braak stages revealed 41 deregulated miRNAs. We focused on miR-132-3p which is strongly altered in both brain areas. Downregulation of this miRNA occurs already at Braak stages III and IV, before loss of neuron-specific miRNAs. Next-generation sequencing confirmed a strong decrease of miR-132-3p and of three family-related miRNAs encoded by the same miRNA cluster on chromosome 17. Deregulation of miR-132-3p in AD brain appears to occur mainly in neurons displaying Tau hyper-phosphorylation. We provide evidence that miR-132-3p may contribute to disease progression through aberrant regulation of mRNA targets in the Tau network. The transcription factor (TF) FOXO1a appears to be a key target of miR-132-3p in this pathway.