Circulating, Cell-Free Micro-RNA Profiles Reflect Discordant Development of Dementia in Monozygotic Twins

J Alzheimers Dis. 2018;63(2):591-601. doi: 10.3233/JAD-171163.

Abstract

We aim to examine if circulating micro-RNA and cytokine levels associate with dementia diagnosis and cognitive scores. To test our hypothesis, we use plasma donated from 48 monozygotic twin pairs in 1997 and 46 micro-RNAs and 10 cytokines were quantified using microfluidic RT-qPCR and multiplex solid-phase immunoassays, respectively. Micro-RNA and cytokine profiling were examined for associations with dementia diagnoses in a longitudinal registry study or with cognitive scores at baseline. Thirty-six micro-RNAs and all cytokines were detected consistently. Micro-RNA profiles associate with diagnoses and cognitive scores at statistically significant levels while cytokine only showed trends pointing at chronic inflammation in twins having or developing dementia. The most notable findings were decreased miR-106a and miR-210, and increased miR-106b expression in twins with a dementia diagnosis. This pioneering evaluation of micro-RNA and cytokine and dementia diagnosis suggests micro-RNA targets in vasculogenesis, lipoprotein transport, and amyloid precursor protein genes.

Keywords: Aging; Alzheimer’s disease; brain; genetics; neurodegenerative.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Circulating MicroRNA / blood*
  • Cross-Sectional Studies
  • Cytokines / blood
  • Dementia / blood*
  • Dementia / immunology
  • Diseases in Twins / blood
  • Diseases in Twins / immunology
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / immunology
  • Longitudinal Studies
  • Male
  • Twins, Monozygotic*

Substances

  • Biomarkers
  • Circulating MicroRNA
  • Cytokines