Exosomal miRNAs as Potential Diagnostic Biomarkers in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD), a neurodegenerative disease, is linked to a variety of internal and external factors present from the early stages of the disease. There are several risk factors related to the pathogenesis of AD, among these exosomes and microRNAs (miRNAs) are of particular importance. Exosomes are nanocarriers released from many different cell types, including neuronal cells. Through the transfer of bioactive molecules, they play an important role both in the maintenance of physiological and in pathological conditions. Exosomes could be carriers of potential biomarkers useful for the assessment of disease progression and for therapeutic applications. miRNAs are small noncoding endogenous RNA sequences active in the regulation of protein expression, and alteration of miRNA expression can result in a dysregulation of key genes and pathways that contribute to disease development. Indeed, the involvement of exosomal miRNAs has been highlighted in various neurodegenerative diseases, and this opens the possibility that dysregulated exosomal miRNA profiles may influence AD disease. The advances in exosome-related biomarker detection in AD are summarized. Finally, in this review, we highlight the use of exosomal miRNAs as essential biomarkers in preclinical and clinical studies in Alzheimer’s disease, also taking a look at their potential clinical value.

Exosomes in Alzheimer’s Disease: From Being Pathological Players to Potential Diagnostics and Therapeutics

“…Non-coding regions on RNA strands (introns) such as miRNA [ 78 ] are regulatory codons involved in protein expression. Furthermore, any alteration in their expression can propagate disease conditions due to dysregulated, non-functioning codons, as in the case of many neurodegenerative disorders [ 79 ]; thus, they can be incorporated into AD gene silencing treatment regimens [ 80 ].…”

Emerging Roles of Exosomes in Huntington’s Disease

“…RNAs and miRNAs enveloped inside the extracellular vesicles are protected from nucleases, therefore they may have long lasting effects on disease related gene expression. In addition, selected exosomal miRNAs have specific profiles in different central nervous system (CNS) disorders even in the presymptomatic stages and their expression significantly changes under the neuropathological conditions, which make them promising biomarkers [ 25 , 26 , 27 ].…”

The Emerging Role of Neural Cell-Derived Exosomes in Intercellular Communication in Health and Neurodegenerative Diseases

“…The levels of inflammatory cytokines and CPs in plasma ADEs of AD patients were significantly higher than those in normal controls, which may be helpful for the early detection of AD (Goetzl et al, 2018b). Gene cargo carried by exosomes also serves as biomarkers for early recognition of AD, in which exosomal miRNAs have been extensively studied and well described in some reviews (Manna et al, 2020;Soares Martins et al, 2021). At present, most studies on exosomal miRNA biomarkers have been carried out in total exosomes without identification of their origin.…”

“…Gene cargo carried by exosomes also serves as biomarkers for early recognition of AD, in which exosomal miRNAs have been extensively studied and well described in some reviews ( Manna et al, 2020 ; Soares Martins et al, 2021 ). At present, most studies on exosomal miRNA biomarkers have been carried out in total exosomes without identification of their origin.…”