The Perspective of Dysregulated LncRNAs in Alzheimer's Disease: A Systematic Scoping Review

Abstract

LncRNAs act as part of non-coding RNAs at high levels of complex and stimulatory configurations in basic molecular mechanisms. Their extensive regulatory activity in the CNS continues on a small scale, from the functions of synapses to large-scale neurodevelopment and cognitive functions, aging, and can be seen in both health and disease situations. One of the vast consequences of the pathological role of dysregulated lncRNAs in the CNS due to their role in a network of regulatory pathways can be manifested in Alzheimer's as a neurodegenerative disease. The disease is characterized by two main hallmarks: amyloid plaques due to the accumulation of β-amyloid components and neurofibrillary tangles (NFT) resulting from the accumulation of phosphorylated tau. Numerous studies in humans, animal models, and various cell lines have revealed the role of lncRNAs in the pathogenesis of Alzheimer's disease. This scoping review was performed with a six-step strategy and based on the Prisma guideline by systematically searching the publications of seven databases. Out of 1,591 records, 69 articles were utterly aligned with the specified inclusion criteria and were summarized in the relevant table. Most of the studies were devoted to BACE1-AS, NEAT1, MALAT1, and SNHG1 lncRNAs, respectively, and about one-third of the studies investigated a unique lncRNA. About 56% of the studies reported up-regulation, and 7% reported down-regulation of lncRNAs expressions. Overall, this study was conducted to investigate the association between lncRNAs and Alzheimer's disease to make a reputable source for further studies and find more molecular therapeutic goals for this disease.

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

“…These findings are in agreement with results of animal model's research considering NEAT1 function involving in epigenetic regulation mechanisms in AD pathology (Asadi et al, 2021[ 4 ]). Huang et al found that lncRNA NEAT1 was elevated during aging in the APP/PS1 mouse model (Huang et al, 2020[ 16 ]).…”

“…Moreover, our findings showed that the plasma lncRNA BC200 level of AD patients was significantly higher than that of healthy controls. Previous research suggested that altered relative BC200 levels up-regulated in the early stages of the disease (Ahmadi et al, 2020[ 2 ]; Asadi et al, 2021[ 4 ]). Similarly, we also found high expression of BC200 in early time point in the course of AD.…”

“…Opposite to these results, Mus et al showed that the expression of BC200 is significantly reduced in brain tissues from patients with AD compared with age-matched normal brains (Mus et al, 2007[ 28 ]). The reason for such discrepancy may be due to differences in brain regions chosen for the analysis and the severity of the disease (Asadi et al, 2021[ 4 ]).…”

Epigenetic Peripheral Biomarkers for Early Diagnosis of Alzheimer’s Disease

“…Interestingly, the authors found that BC200 levels are significantly increased in the plasma of preclinical-AD subjects compared with the control group, suggesting it as promising biomarker in the early detection of the disease [ 101 ]. These findings are in agreement with previous research suggesting upregulated BC200 levels in the early stage of AD [ 106 , 107 ].…”

LncRNAs as the Regulators of Brain Function and Therapeutic Targets for Alzheimer’s Disease

“…Admittedly, there are still many challenges in this area that need to be overcome. Although a large number of dysregulated AD-associated lncRNAs [ 133 ] were identified, the functional characterization of most lncRNAs is still lacking, and it is a huge challenge to identify functionally important lncRNAs from multiple recorded non-coding transcripts. Thus, a comprehensive functional characterization of lncRNAs would be the logical next step.…”