The Potential Markers of Circulating microRNAs and long non-coding RNAs in Alzheimer's Disease

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder and one of the leading causes of disability and mortality in the late life with no curative treatment currently. Thus, it is urgently to establish sensitive and non-invasive biomarkers for AD diagnosis, particularly in the early stage. Recently, emerging number of microRNAs (miRNAs) and long-noncoding RNAs (lncRNAs) are considered as effective biomarkers in various diseases as they possess characteristics of stable, resistant to RNAase digestion and many extreme conditions in circulatory fluid. This review highlights recent advances in the identification of the aberrantly expressed miRNAs and lncRNAs in circulatory network for detection of AD. We summarized the abnormal expressed miRNAs in blood and cerebrospinal fluid (CSF), and detailed discussed the functions and molecular mechanism of serum or plasma miRNAs-miR-195, miR-155, miR-34a, miR-9, miR-206, miR-125b and miR-29 in the regulation of AD progression. In addition, we also elaborated the role of circulating lncRNA major including beta-site APP cleaving enzyme 1 (BACE1) and its antisense lncRNA BACE1-AS in AD pathological advancement. In brief, confirming the aberrantly expressed circulating miRNAs and lncRNAs will provide an effective testing tools for treatment of AD in the future.

microRNA-146a Signaling in Alzheimer's Disease (AD) and Prion Disease (PrD)

“…These same data suggest that a significant pathological upregulation of NF-kB (p50/p65)-miRNA-146a signaling coupled to downregulation of pathogenic mRNA targets such as IRAK and CFH may directly contribute to altered innate-immune or inflammatory responses in both viral-and prion-mediated infections, features that also accompany progressive, irreversible inflammatory neurodegeneration in a surprisingly wide range of human brain diseases including AD and PrD and in murine transgenic models for these diseases. Currently, there is (i) considerable research effort involving miRNA-based pre-symptomatic predictive and/or diagnostic biomarkers in the cerebrospinal fluid (CSF) and blood serum of the systemic circulation; and (ii) related therapeutic opportunities that address a wide range of these insidious, progressive, and lethal neurological disorders in which signaling along the NF-kB-miRNA-146a axis appears to be playing a critical role in brain cell fate (8,9,24,56). Although much of the data obtained to date are relatively preliminary and need to be further confirmed in suitable brain cell-culture models, transgenic animal model studies, and controlled clinical trials, they draw considerable and thought-provoking attention to a rapidly evolving field of neurobiology and neurogenetics that should acquire increasing relevance in the future as to the nature of the pathogenic signaling mechanisms involved in these insidious and lethal neuropathological states.…”

Predictive Potential of Circulating Ube2h mRNA as an E2 Ubiquitin-Conjugating Enzyme for Diagnosis or Treatment of Alzheimer’s Disease

“…In addition, the diagnosis of AD is dependent on the disease progression and biomarker profiles. However, the onset and progression of AD in patients is clinically variable, and biomarker assessment and the molecular mechanisms remain poorly understood [26]. Most of all, the limitations of these approaches are due to the lack of knowledge about AD.…”

Downregulated Platelet miR-1233-5p in Patients with Alzheimer’s Pathologic Change with Mild Cognitive Impairment is Associated with Aβ-Induced Platelet Activation via P-Selectin

“…As miRNAs can be secreted or excreted into the extracellular space [38] and are detectable in plasma and serum, such circulating miRNAs have emerged as minimally invasive biomarkers. Indeed, various serum miRNAs, including miR-342-3p, miR-195, miR-155, miR-9, miR-206, and miR-29, are recently suggested as promising diagnostic markers for AD [39,40]. Nevertheless, it has also been recognized that serum/plasma profiles for AD-related markers are difficult to reproduce [41] because factors such as accompanying inflammation are likely to influence the plasma levels of these markers.…”