Beta-Amyloid-Dependent miRNAs as Circulating Biomarkers in Alzheimer's Disease: a Preliminary Report

J Mol Neurosci. 2020 Jun;70(6):871-877. doi: 10.1007/s12031-020-01511-0. Epub 2020 Apr 18.

Abstract

MicroRNAs (miRNAs) are considered among the most reliable biomarkers to diagnose and predict Alzheimer's disease (AD), due to their regulatory nature. The main goal of this study was to evaluate the expression of miR4422 and miR3714, as the main regulators of GSAP and BACE1 expression, in AD patients compared with healthy subjects. Twenty patients with a mild to moderate AD (58-71 years old) and 15 healthy subjects (58-73 years old) participated in this study. The expression levels of miR4422 and miR3714 as the target genes and 5S rRNA and miRlet7a-5p as the reference genes were measured in the two groups. To compare the expression between the case and the control groups, the t test or the Wilcoxon test was used, based on the data distribution patterns. The efficiencies of amplification of the miR4422, miR3714, 5S rRNA, and miRlet7a-5p genes all were in the acceptable range. The mean miR4422-5S rRNA dCt value was significantly different between the two groups (p = 0.018). The relative fold change of the expression was 0.43. The mean miR4422-miRlet7a-5p dCt value (p = 0.41), the mean miR3714-5S rRNA dCt value (p = 0.10), and the mean miR3714-miRlet7a-5p dCt value (p = 0.063) were not significantly different between the two groups. We indicated that miR4422 could be a reliable biomarker for Alzheimer's diagnosis. It seems that the reduced expression of miR4422 that targets GSAP and BACE1 expression can lead to an increase in the formation of Aβ plaque.

Keywords: Alzheimer’s disease; BACE1; Biomarker; GSAP; miRNA.

MeSH terms

  • Aged
  • Alzheimer Disease / blood*
  • Alzheimer Disease / pathology
  • Amyloid Precursor Protein Secretases / genetics
  • Amyloid Precursor Protein Secretases / metabolism
  • Amyloid beta-Peptides / metabolism
  • Aspartic Acid Endopeptidases / genetics
  • Aspartic Acid Endopeptidases / metabolism
  • Biomarkers / blood
  • Circulating MicroRNA / blood*
  • Circulating MicroRNA / genetics
  • Circulating MicroRNA / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Proteins / genetics
  • Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Circulating MicroRNA
  • GSAP protein, human
  • Proteins
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human