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.
Highlights
The fact that patients with Alzheimer’s disease (AD) are characterized by alterations of miRNAs in biological fluids, and many of their target genes such as presenilins, BACE-1, amyloid precursor protein (APP) are directly involved in the pathophysiology of AD, generates great interest in the research of the mechanisms involved in the regulation of target genes belonging to the main pathways affected by AD, such as neuroinflammation, neurodegeneration, neurogenesis, oxidative response and neuronal plasticity
The presence in peripheral body fluids, such as CSF and serum, of molecules that could act as biomarkers for the diagnosis of neurodegenerative diseases has become an active area of research
As CSF is directly in contact with the extracellular space of the brain and can mirror the biochemical alterations that occur in the brain, it is an optimal source of AD biomarkers, and circulating miRNAs are attractive candidates for monitoring disease
Summary
Alzheimer’s disease (AD), the most common cause of dementia, is a neurodegenerative disorder that exhibits loss of synapses, extracellular amyloid plaques formed by the amyloid-β peptide (Aβ) and endocellular aggregates of the hyperphosphorylated tau protein. The presence of neuronal plaques triggers an inflammatory process mediated by astrocytes and microglia with consequent induction of the immune response, which entails the production of cytokines, interleukins and TNF-alpha, by macrophages and neutrophils, irreversibly damaging the neurons [7,8] This primary response represents a kind of protection for the brain, it is thought that this prolonged state of chronic inflammation may be the basis of neuronal degeneration. Another major injury affecting the pathogenesis of AD is the formation of neurofibrillary tangles, which derive from the aggregation of the hyperphosphorylated forms of the tau protein; a protein that promotes the assembly and stabilization of microtubules. Its phosphorylation by some protein kinases, such as GSK-3β and Cdk-5, causes detachment from microtubules and further phosphorylation events, or the lack of dephosphorylation causes a conformational change that induces aggregation and formation of neurofibrillary tangles resulting in neuronal death [9]
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