Plasma microRNA vary in association with the progression of Alzheimer's disease

Abstract

Introduction Early intervention in Alzheimer's disease (AD) requires the development of an easily administered test that is able to identify those at risk. Focusing on microRNA robustly detected in plasma and standardizing the analysis strategy, we sought to identify disease‐stage specific biomarkers. Methods Using TaqMan microfluidics arrays and a statistical consensus approach, we assessed plasma levels of 185 neurodegeneration‐related microRNA, in cohorts of cognitively normal amyloid β‐positive (CN‐Aβ+), mild cognitive impairment (MCI), and Alzheimer's disease (AD) participants, relative to their respective controls. Results Distinct disease stage microRNA biomarkers were identified, shown to predict membership of the groups (area under the curve [AUC] >0.8) and were altered dynamically with AD progression in a longitudinal study. Bioinformatics demonstrated that these microRNA target known AD‐related pathways, such as the Phosphoinositide 3‐kinase (PI3K‐Akt) signalling pathway. Furthermore, a significant correlation was found between miR‐27a‐3p, miR‐27b‐3p, and miR‐324‐5p and amyloid beta load. Discussion Our results show that microRNA signatures alter throughout the progression of AD, reflect the underlying disease pathology, and may prove to be useful diagnostic markers.

Beyond CSF and Neuroimaging Assessment: Evaluating Plasma miR-145-5p as a Potential Biomarker for Mild Cognitive Impairment and Alzheimer’s Disease

“…Even with different analysis approaches, there is one common serum miRNA (miR-143–3p), and it was shown that inhibition of this miRNA might promote neuronal survival according to an AD cell model . In another study, a significant association among miR-27a-3p, miR-27b-3p, and miR-324–5p and Aβ loads among cognitively normal Aβ-positive, MCI, and AD participants was identified . No overlapping miRNAs were found, possibly due to different populations, disease stages, and study design.…”

“…Furthermore, it has been suggested that plasma miRNA levels change before the onset of symptoms and vary dynamically with disease progression. 31 There has been increasing evidence suggesting that the PI3K/ AKT pathway plays a key role in the pathophysiology of AD. 56,59,63 This pathway governs a multitude of biological processes, including cell proliferation, motility, growth, survival, and metabolic functions, while also acting to inhibit numerous neurotoxic mechanisms.…”

“…However, these miRNAs also target the PI3K/AKT signaling pathway, which is consistent with the process identified in our study. Furthermore, it has been suggested that plasma miRNA levels change before the onset of symptoms and vary dynamically with disease progression …”

“…Additionally, miRNAs have been implicated in neuronal apoptosis regulation and attenuation of Aβ neurotoxicity 29,30 and it has been reported that plasma miRNAs are altered prior to the occurrence of symptoms. 31 Several studies have focused on identifying consistent circulating miRNA signature for AD; 32−35 however, so far, few results were concordant.…”

“…Growing evidence suggests that microRNAs (miRNAs), which are a class of noncoding RNAs that regulates gene expression at the post-transcriptional level, can be potential biomarkers for AD. − Moreover, it has been shown that excreted circulating miRNAs can cross the blood–brain barrier, indicating its potential as biomarkers for neurodegenerative diseases. Additionally, miRNAs have been implicated in neuronal apoptosis regulation and attenuation of Aβ neurotoxicity , and it has been reported that plasma miRNAs are altered prior to the occurrence of symptoms . Several studies have focused on identifying consistent circulating miRNA signature for AD; − however, so far, few results were concordant.…”