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

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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.

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Funding

This work was supported by the Cognitive Sciences and Technologies Council of Iran, grant number 2717.

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Authors and Affiliations

  1. Department of Animal Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran

    Seyedeh Nahid Fotuhi, Mohammad Khalaj-Kondori & Mohammad Ali Hoseinpour Feizi

  2. Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Mahnaz Talebi

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  1. Seyedeh Nahid Fotuhi
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  2. Mohammad Khalaj-Kondori
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  3. Mohammad Ali Hoseinpour Feizi
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  4. Mahnaz Talebi
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Correspondence to Mohammad Khalaj-Kondori.

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Fotuhi, S.N., Khalaj-Kondori, M., Hoseinpour Feizi, M.A. et al. Long Non-coding RNA BACE1-AS May Serve as an Alzheimer’s Disease Blood-Based Biomarker. J Mol Neurosci 69, 351–359 (2019). https://doi.org/10.1007/s12031-019-01364-2

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