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

• Published in: Journal of molecular neuroscience Vol. 69; no. 3; pp. 351 - 359
• Main Authors: Fotuhi, Seyedeh Nahid, Khalaj-Kondori, Mohammad, Hoseinpour Feizi, Mohammad Ali, Talebi, Mahnaz
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.11.2019; Springer Nature B.V
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - blood; Alzheimer Disease - genetics; Alzheimer Disease - psychology; Alzheimer's disease; Apolipoproteins E - genetics; Biomarkers; Biomedical and Life Sciences; Biomedicine; Blood; Blood circulation; Brain; Cell Biology; Exosomes; Exosomes - chemistry; Exosomes - ultrastructure; Female; Humans; Light scattering; Male; Mental Status and Dementia Tests; Microscopy, Electron, Scanning; Neurochemistry; Neurology; Neurosciences; Non-coding RNA; Photon correlation spectroscopy; Plasma; Proteomics; Reagents; Real-Time Polymerase Chain Reaction; RNA - blood; RNA, Long Noncoding - blood; ROC Curve; Scanning electron microscopy; Sensitivity; Sensitivity and Specificity; Subgroups; β-Site APP-cleaving enzyme 1; Biomarker; Alzheimer’s disease; BACE1-AS; Exosome; Early detection
• DOI: 10.1007/s12031-019-01364-2
• ISSN: 0895-8696; 1559-1166

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.