CSF microRNA Profiling in Alzheimer's Disease: a Screening and Validation Study

Mol Neurobiol. 2017 Nov;54(9):6647-6654. doi: 10.1007/s12035-016-0106-x. Epub 2016 Oct 13.

Abstract

MicroRNAs (miRNAs) are short non-coding RNA molecules that regulate gene expression through post-transcriptional repression of target genes. They have been shown to be implicated in the pathophysiology of Alzheimer's disease (AD) and proposed as disease biomarkers. In the present work, we have studied the expression levels of 754 miRNAs in cerebrospinal fluid (CSF) from AD patients and control subjects. We have explored a first screening cohort (N = 20) and selected 12 miRNAs to be further tested in a second independent validation cohort (N = 69). We have found a significant upregulation of miR-222 and miR-125b in AD CSF. Of these, the association of miR-222 with AD is novel and reported here for the first time whereas upregulation of miR-125b has been previously reported in AD brain. Yet we do not find association with other miRNAs which were previously linked to AD. Our results shed light on potential underlying pathophysiological processes of AD and also point out the need for consensus procedures in CSF miRNA detection and data analysis.

Keywords: Alzheimer’s disease; Biomarkers; Cerebrospinal fluid; miR-125b; miR-222; microRNAs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / genetics*
  • Biomarkers / cerebrospinal fluid
  • Brain / metabolism
  • Cohort Studies
  • Female
  • Genetic Testing / methods
  • Genetic Testing / standards
  • Humans
  • Male
  • MicroRNAs / biosynthesis
  • MicroRNAs / cerebrospinal fluid*
  • MicroRNAs / genetics*
  • Middle Aged

Substances

  • Biomarkers
  • MIRN125 microRNA, human
  • MIRN222 microRNA, human
  • MicroRNAs