Alteration of the microRNA network during the progression of Alzheimer's disease

EMBO Mol Med. 2013 Oct;5(10):1613-34. doi: 10.1002/emmm.201201974. Epub 2013 Sep 9.


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.

Keywords: Alzheimer's disease; hippocampus; miR-132-3p; microRNA; prefrontal cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Area Under Curve
  • Brain / metabolism
  • Chromosomes, Human, Pair 17
  • Cluster Analysis
  • Cohort Studies
  • Disease Progression
  • Down-Regulation
  • Gene Expression Profiling
  • High-Throughput Nucleotide Sequencing
  • Hippocampus / metabolism
  • Humans
  • MicroRNAs / metabolism*
  • Neurons / metabolism
  • Phosphorylation
  • ROC Curve
  • Severity of Illness Index
  • tau Proteins / metabolism


  • MIRN132 microRNA, human
  • MicroRNAs
  • tau Proteins