Journal
EMBO MOLECULAR MEDICINE
Volume 5, Issue 10, Pages 1613-1634Publisher
WILEY
DOI: 10.1002/emmm.201201974
Keywords
Alzheimer's disease; hippocampus; prefrontal cortex; microRNA; miR-132-3p
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Funding
- Marie-Curie International Incoming Fellowship grant
- Top Institute Pharma [T5-207]
- Arthur Bax-Anna Vanluffelen chair for Alzheimer research
- European Research Council (ERC)
- Queen Elisabeth Foundation
- Fonds voor wetenschappelijk onderzoek (FWO)
- KULeuven
- VIB
- Interuniversity Attraction Poles Program of the Belgian Federal Science Policy Office [IUAP P6P7/1658]
- Flemish Government
- Teva pre-doctoral fellowship
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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.
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