miR-146a and miR-181a are involved in the progression of mild cognitive impairment to Alzheimer's disease: Neurobiology of Aging

A. Ansari, E. Maffioletti, E. Milanesi, M. Marizzoni, G.B. Frisoni, O. Blin, J.C. Richardson, R. Bordet, G. Forloni, M. Gennarelli, L. Bocchio-Chiavetto, PharmaCog Consortium

Research output: Contribution to journalArticle

Abstract

The identification of mechanisms associated with Alzheimer's disease (AD) development in mild cognitive impairment (MCI) would be of great usefulness to clarify AD pathogenesis and to develop preventive and therapeutic strategies. In this study, blood levels of the candidate microRNAs (small noncoding RNAs that play a pivotal role in gene expression) miR-146a, miR-181a, miR-181b, miR-24-3p, miR-186a, miR-101, miR-339, miR-590, and miR-22 have been investigated for association to AD conversion within 2 years in a group of 45 patients with MCI. Baseline miR-146a (p = 0.036) and miR-181a (p = 0.026) showed a significant upregulation in patients with MCI who later converted to AD. These alterations were related to AD hallmarks: a significant negative correlation was found with amyloid beta cerebrospinal fluid concentration for miR-146a (p = 0.006) and miR-181a (p = 0.001). Moreover, higher levels of miR-146a were associated to apolipoprotein E ε4 allele presence, smaller volume of the hippocampus (p = 0.045) and of the CA1 (p = 0.013) and the subiculum (p = 0.027) subfields. Increased levels of miR-146a (p = 0.031) and miR-181a (p = 0.002) were also linked with diffusivity alterations in the cingulum. These data support a role for miR-146a and miR-181a in the mechanisms of AD progression. © 2019 Elsevier Inc.
Original languageEnglish
Pages (from-to)102-109
Number of pages8
JournalNeurobiol. Aging
Volume82
DOIs
Publication statusPublished - 2019

Keywords

  • AD
  • Alzheimer's disease
  • MCI
  • microRNA
  • Mild cognitive impairment
  • miR-146a
  • miR-181a
  • Whole blood
  • amyloid beta protein
  • microRNA 101
  • microRNA 146a
  • microRNA 181
  • microRNA 181b
  • microRNA 186a
  • microRNA 22
  • microRNA 24 3p
  • microRNA 339
  • microRNA 590
  • unclassified drug
  • aged
  • Alzheimer disease
  • Article
  • cingulum (brain)
  • clinical article
  • cohort analysis
  • controlled study
  • disease course
  • female
  • hippocampal CA1 region
  • human
  • male
  • mild cognitive impairment
  • Mini Mental State Examination
  • pathogenesis
  • priority journal
  • protein cerebrospinal fluid level
  • reverse transcription polymerase chain reaction
  • subiculum

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