Plasma lncRNA profiling identified BC200 and NEAT1 lncRNAs as potential blood-based biomarkers for late-onset Alzheimer’s disease

Abstract

Long non-coding RNAs (lncRNA) play critical roles in pathogenesis of neurodegenerative diseases. Human plasma carries lncRNAs that are stable in the blood, and their disease-specific profile have made them valuable biomarkers for some diseases. This study reports screening of the plasma levels of 90 lncRNAs in patients with Alzheimer disease (AD) to find out plasma-based AD biomarkers. Total RNA was isolated from plasma samples of 50 AD and 50 matched healthy controls. The plasma samples of 10 advanced AD patients and 10 matched healthy controls were screened for expression levels of 90 lncRNAs using Human LncRNA Profiler qPCR Array Kit (SBI). Based on the profiling results, lncRNAs BC200, NDM29, NEAT1, FAS-AS1 and GAS5-AS1 were selected for further analysis in all samples and their biomarker potency was evaluated by ROC curve analysis. We further surveyed RNAseq data by in silico analysis. We found that the NEAT1 and BC200 levels in the plasma of the AD patients were significantly higher compared with the control group (P=0.0021, p= 0.02, respectively). ROC curve analysis showed that the plasma level of NEAT1 and BC200 discriminated AD patients from healthy controls with sensitivity of 72 % and 60 %, and specificity of 84 % and 91 % respectively. Moreover, NEAT1 discriminated MCI (60 % sensitivity and 91 % specificity) and advanced-AD patients from healthy controls (73 % sensitivity and 71 % specificity). Besides, plasma level of BC200 discriminated the pre-clinical subjects from healthy controls with 83 % sensitivity and 66 % specificity. A positive correlation was also observed between plasma levels of BC200 with the age patients (r = 0.34, p=0.02). In silico RNAseq data analysis showed that a total of 33 lncRNAs were up-regulated but 13 lncRNAs were down-regulated significantly in AD patients compared with the healthy controls. In conclusion, this study elucidated that the plasma levels of lncRNAs NEAT1 and BC200 might be considered as potential blood-based biomarkers for AD development and progression.

Circulating long non-coding RNAs as novel diagnostic biomarkers for Alzheimer’s disease (AD): A systematic review and meta-analysis

“…Among seven lncRNAs, three lncRNAs were reported to be upregulated (RNA BACE-AS1, RNA NEAT1, RNA GAS5) [ 22 , 30 , 31 , 34 ]. BACE1-AS lncRNA was confirmed in more than one study as significantly upregulated in plasma samples [ 22 , 31 , 32 ].…”

“…Moreover, RNA 51A and RNA BC200 were reported to have variable expression patterns. Deng et al and Khodayi et al reported, respectively, significant upregulation of RNA 51A and BC200 in the plasma of AD patients compared to healthy controls [ 32 , 34 ]. However, Feng et al [ 30 ] and Wang et al [ 31 ] did not find any significant difference between AD and healthy controls regarding 51A and BC200 lncRNA.…”

Insights into the mechanisms of non-coding RNAs’ implication in the pathogenesis of Alzheimer’s disease

“…They also showed that BC200 might be a potent positive regulator of BACE1, and could reduce apoptosis and increase viability of the AD cells (Li et al, 2018[ 74 ]). Remarkably, BC200 plasma levels have recently been reported to be higher in AD patients, implying its potential as a blood-based biomarker for early diagnosis of AD (Khodayi et al, 2022[ 64 ]).…”

Long Non-coding RNAs, Extracellular Vesicles and Inflammation in Alzheimer’s Disease

“…The mechanism of action of BC200 involves the PI3K/AKT axis found both in cancer cells [65] and in an AD model, associated with inflammation [66]. Interestingly, plasma BC200 has been found to be able to discriminate healthy controls from preclinical cases [67].…”