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

Abstract

Alzheimer’s Disease (AD) has currently no effective treatment; however, preventive measures have the potential to reduce AD risk. Thus, accurate and early prediction of risk is an important strategy to alleviate the AD burden. Neuroinflammation is a major factor prompting the onset of the disease. Inflammation exerts its toxic effect via multiple mechanisms. Amongst others, it is affecting gene expression via modulation of non-coding RNAs (ncRNAs), such as miRNAs. Recent evidence supports that inflammation can also affect long non-coding RNA (lncRNA) expression. While the association between miRNAs and inflammation in AD has been studied, the role of lncRNAs in neurodegenerative diseases has been less explored. In this review, we focus on lncRNAs and inflammation in the context of AD. Furthermore, since plasma-isolated extracellular vesicles (EVs) are increasingly recognized as an effective monitoring strategy for brain pathologies, we have focused on the studies reporting dysregulated lncRNAs in EVs isolated from AD patients and controls. The revised literature shows a positive association between pro-inflammatory lncRNAs and AD. However, the reports evaluating lncRNA alterations in EVs isolated from the plasma of patients and controls, although still limited, confirm the value of specific lncRNAs associated with AD as reliable biomarkers. This is an emerging field that will open new avenues to improve risk prediction and patient stratification, and may lead to the discovery of potential novel therapeutic targets for AD.

The Role of Tau Pathology in Alzheimer’s Disease and Down Syndrome

“…A recent meta-analysis combining genome-wide association studies (GWAS) expanded the number of AD-risk loci, but most disease-associated variants reside in non-protein coding regions of the genome, such as in long non-coding (lnc) RNAs [ 58 ]. LncRNAs contribute to the pathogenesis of AD via modulating amyloid production, Tau hyperphosphorylation, mitochondrial dysfunction, oxidative stress, synaptic impairment and neuroinflammation, and have been thoroughly reviewed previously [ 59 , 60 , 61 , 62 ]. With lncRNA, several therapeutic approaches have been built around competing with endogenous RNA modulation [ 63 ], and determining whether or not various modulation technologies will be effective in physiological contexts remains a high-priority research agenda.…”

Roles of HOTAIR Long Non-coding RNA in Gliomas and Other CNS Disorders

“…This is changing as evidenced by the recent surge in studies proposing lncRNAs, including HOTAIR as important mediators of different aspects of non-oncological CNS disorders (Fig. 3 ), such as neurodegeneration, psychiatric illnesses, and developmental conditions (Li et al 2020 ; Wu and Kuo 2020 ; Canseco-Rodriguez et al 2022 ). This section first considers the different non-oncological neuronal pathways influenced by HOTAIR lncRNA.…”

Research progress on the role of extracellular vesicles in neurodegenerative diseases

“…In AD, changes in EV miRNAs that target APP processing, tau phosphorylation, and mitochondrial- and apoptosis-related genes that regulate neurodegenerative events in AD, have received much attention [ 102 ]. A recent study has shown that SNORDs–a group of Box C/D small nucleolar RNAs – are enriched differently in EVs isolated from the plasma of AD patients compared to controls [ 103 ].…”