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

Background and Aim : The use of diagnostic agents to diagnose the onset of Alzheimer s disease (AD) and the rate of progression for appropriate treatment has become an essential requirement. The change in BACE1 transcript level is one of the most important causes of AD, which is strongly controlled by BACE1-AS. They have a significant increase in the cerebrospinal fluid of Alzheimer s patients. This increase can be used as a diagnostic factor for the detection of AD. The aim of this study was to detect the presence of BACS1-AS lncRNA in blood serum and plasma-derived exosomes of people with AD. Also, with its confirmation in serum and exosomes, the biomarker potency of BACE1-AS was estimated.Methods : For this purpose, blood samples were collected from 45 patients and 36 non-addicted patients. Total RNA was extracted. The plasma of blood samples was isolated and plasma RNA was extracted with TRIzol extraction solution. In the second part of the work, exosomes were purified from the plasma samples using Exoqiuck extraction solution. The exosome extraction was confirmed with SEM and DLS. Then, the RNAs of exosomes were isolated. To synthesize cDNA from the RNA of plasma and exosomal samples, the TaKaRa synthesis kits were used. With existing cDNAs, the primers of the BACE1-AS gene and the U6 gene (internal control) were evaluated in terms of temperature and assure the correct functioning of the primers. BACE1-AS gene expression was evaluated quantitatively using Quantitative Real-Time and the data were analyzed with SPSS software.Results : The presence of the BACE1-AS transcript was confirmed in plasma and exosomal specimens. BACE1-AS transcript expression level did not change between patient and control groups of plasma samples and exosomal samples extracted from human plasma. The expression level of BACE1-AS between Alzheimer s subgroup (Full-AD) and control (p <0.0001), Alzheimer subset (Full-AD) and pre-AD (p <0.0001) and Alzheimer subset (Pre-AD) ) And the control group (p <0.0001) was significant. The level of BACE1-AS transcript increases between Alzheimer s sub-group (Full-AD) and control. The expression level of BACE1-AS in the Alzheimer s subgroup (Full-AD) is higher than the pre-AD pre-Alzheimer s. However, the level of expression in the pre-AD subgroup is lower than that of the control group. By analyzing BACE1-AS transcriptase in exosomal samples, it was determined that expression of this gene between Alzheimer s subgroup (Full-AD) and control, Alzheimer s subset (Full-AD) and Pre-Alzheimer s (Pre-AD) subgroups - Alzheimer s (Pre-AD) and control group are not significant. The biomarker potency of BACE1-AS in human plasma samples showed a 98% sensitivity and 100% specificity of this gene in the Alzheimer s subtype (Full-AD) and control. Also, the biomarker potency of this gene indicates a sensitivity of 99% and a 100% specificity between the Alzheimer s subtype (Full-AD) and Alzheimer s pre-AD (Pre-AD). BACE1-AS shows the sensitivity is 68% and the specificity is 100% Between the pre-Alzheimer (pre-AD) subset and control.Conclusion : Compared to blood-derived exosome, plasma-based BACE1-AS is a potential biomarker to differentiate Alzheimer s disease from the control, Alzheimer s from the pre-Alzheimer group and the pre-Alzheimer s group from the control.

کلیدواژه ها:

Alzheimer’s disease ، BACE1-AS ، Biomarker ، Exosome ، Early detection