Validation of microRNAs in Cerebrospinal Fluid as Biomarkers for Different Forms of Dementia in a Multicenter Study

J Alzheimers Dis. 2016 Apr 16;52(4):1321-33. doi: 10.3233/JAD-160038.

Abstract

MicroRNAs (miRNAs) regulate translational inhibition of proteins, but are also detected in body fluids, including cerebrospinal fluid (CSF), where they may serve as disease-specific biomarkers. Previously, we showed differential expression of miR-146a, miR-29a, and miR-125b in the CSF of Alzheimer's disease (AD) patients versus controls. In this study, we aim to confirm these findings by using larger, independent sample cohorts of AD patients and controls from three different centers. Furthermore, we aim to identify confounding factors that possibly arise using such a multicenter approach. The study was extended by including patients diagnosed with mild cognitive impairment due to AD, frontotemporal dementia and dementia with Lewy bodies. Previous results of decreased miR-146a levels in AD patients compared to controls were confirmed in one center. When samples from all three centers were combined, several confounding factors were identified. After controlling for these factors, we did not identify differences in miRNA levels between the different groups. However, we provide suggestions to circumvent various pitfalls when measuring miRNAs in CSF to improve future studies.

Keywords: Alzheimer’s disease; Lewy body disease; cerebrospinal fluid; frontotemporal dementia; microRNAs; mild cognitive impairment.

Publication types

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

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid
  • Case-Control Studies
  • Cognitive Dysfunction / cerebrospinal fluid
  • Dementia / cerebrospinal fluid*
  • Disease Progression
  • Female
  • Frontotemporal Dementia / cerebrospinal fluid
  • Humans
  • Lewy Body Disease / cerebrospinal fluid
  • Male
  • MicroRNAs / cerebrospinal fluid*
  • Middle Aged

Substances

  • Biomarkers
  • MIRN125 microRNA, human
  • MIRN146 microRNA, human
  • MIRN29 microRNA, human
  • MicroRNAs