Long Non-coding RNA BACE1-AS May Serve as an Alzheimer's Disease Blood-Based Biomarker

J Mol Neurosci. 2019 Nov;69(3):351-359. doi: 10.1007/s12031-019-01364-2. Epub 2019 Jul 1.

Abstract

Circulating long noncoding RNAs (lncRNAs) might serve as biomarkers for different pathological conditions. BACE1-AS lncRNA upregulates in the brain of people with Alzheimer's disease (AD) and might be detected in the bloodstream. To reveal if lncRNA BACE1-AS may serve as a blood-based biomarker for AD, we compared its levels in plasma and plasma-derived exosomes between AD (n = 45) and healthy people (n = 36). Exosomes were purified from plasma by Invitrogen™ Total Exosome Isolation Kit and characterized by scanning electron microscopy (SEM) and dynamic light scattering (DLS). Total RNA was extracted from whole plasma, and plasma-derived exosomes using TRIzol® LS or TRIzol® Reagents respectively were then reverse transcribed to the cDNA using PrimeScript II cDNA synthesis kit. The BACE1-AS levels were quantified by real-time PCR, and their biomarker potencies were evaluated using ROC curve analysis. Results obtained verified the presence of BACE1-AS in the plasma samples of both AD and healthy controls. We did not observe any significant differences between the levels of BACE1-AS in the plasma or plasma-derived exosomes of AD and control people. However, there were significant differences between AD subgroups and control in the whole plasma samples. The BACE1-AS level was low in pre-AD subgroup but it was high in full-AD people compared to the healthy controls. Moreover, ROC curve analysis revealed that lncRNA BACE1-AS may discriminate pre-AD and healthy control (75% sensitivity and 100% specificity), full-AD and healthy control (68% sensitivity and 100% specificity), and pre-AD and full-AD subgroups (78% sensitivity and 100% specificity), highlighting its potential as a biomarker for AD development. In conclusion, plasma BACE1-AS level may serve as a potent blood-based biomarker for Alzheimer's disease.

Keywords: Alzheimer’s disease; BACE1-AS; Biomarker; Early detection; Exosome.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / psychology
  • Apolipoproteins E / genetics
  • Biomarkers
  • Exosomes / chemistry
  • Exosomes / ultrastructure
  • Female
  • Humans
  • Male
  • Mental Status and Dementia Tests
  • Microscopy, Electron, Scanning
  • RNA / blood
  • RNA, Long Noncoding / blood*
  • ROC Curve
  • Real-Time Polymerase Chain Reaction
  • Sensitivity and Specificity

Substances

  • Apolipoproteins E
  • BACE1-AS long non-coding RNA, human
  • Biomarkers
  • RNA, Long Noncoding
  • RNA