Peripheral Blood MicroRNA Expression Profiles in Alzheimer's Disease: Screening, Validation, Association with Clinical Phenotype and Implications for Molecular Mechanism

Mol Neurobiol. 2016 Oct;53(8):5772-81. doi: 10.1007/s12035-015-9484-8. Epub 2015 Oct 26.

Abstract

A series of investigations have been performed regarding microRNA (miRNA, miR) of Alzheimer's disease (AD) patients. However, most of these used microarray with neither validation by PCR nor any follow-up on the biological mechanism implicated by findings. Further, there were rarely any analyses linking clinical phenotype of de novo, drug-naive patients to cellular pathogenic mechanism(s) to date. Microarray screening followed by validation via quantitative PCR (Q-PCR) assays and the relationship between miRNAs and phenotypic indices were evaluated. Additionally, the cellular mechanism of miRNAs through effects of β-site amyloid precursor protein (APP) cleaving enzyme (BACE1) was assessed. We identified 2 specific differentially expressed (DE) miRNAs (miR-339 and miR-425) as potential diagnostic biomarkers for AD and revealed that these DE miRNAs could be involved in modulating the pathogenesis of AD via BACE1 protein inhibition. The findings presented here reveal a detailed snapshot of the profile of peripheral blood mononuclear cells (PBMC) miRNA changes in AD patients, association with clinical phenotype, and potential roles in cellular pathogenesis.

Keywords: Alzheimer’s disease; Expression profiles; MicroRNA; β-site APP cleaving enzyme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Aged
  • Alzheimer Disease / blood*
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / genetics*
  • Amyloid Precursor Protein Secretases / metabolism
  • Aspartic Acid Endopeptidases / metabolism
  • Base Sequence
  • Case-Control Studies
  • Cluster Analysis
  • Gene Expression Profiling*
  • Humans
  • Mass Screening*
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • Phenotype
  • ROC Curve
  • Reproducibility of Results

Substances

  • 3' Untranslated Regions
  • MicroRNAs
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human