miRNA-Based Signature to Predict the Development of Alzheimer’s Disease

Abstract

Background: Background: Patients with mild cognitive impairment (MCI) suffer from high risk of developing Alzheimer’s disease (AD). Cumulative evidence has demonstrated that development of AD is a complex process which could be modulated by miRNAs. Here, we aimed to identify miRNAs involved in the pathway, and interrogate their ability to predict prognosis in patients with MCI. Methods: Methods: We obtained the miRNA-seq profiles and the clinical characteristics of patients with MCI from the Gene Expression Omnibus (GEO). Cox regression analysis was used to construct a risk level model. Receiver operating characteristic (ROC) curve was used to assess performance of the model for predicting prognosis. Combined with clinical characteristics, factors associated with prognosis were identified and a predictive prognosis nomogram was developed and validated. Through Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we evaluated molecular signatures for the candidate miRNAs. Results: Results: Our analysis identified 120 DEmiRNAs. The Cox regression analysis showed that two miRNAs could serve as risk factors for disease development. A risk level model was constructed. Age, apoe4 and risk level were associated with the prognosis. We developed a nomogram to predict disease progression. Calibration curve and concordance index (C-index) demonstrated the reliability of the nomogram. Functional enrichment analysis showed that these miRNAs were involved in regulating both cGMP−PKG and Sphingolipid signaling pathways. Conclusion: Conclusion: We have identified miRNAs associated with the development of MCI. These miRNAs could be used for early diagnosis, and surveillance in patients with MCI, enabling prediction of the development of AD.

Exploring small non-coding RNAs as blood-based biomarkers to predict Alzheimer’s disease

“…Due to their role as genetic regulators, miRNAs are nowadays considered potential therapeutic tools for restoring cell functions disrupted during disease progression [ 14 – 16 ]. Previous studies have shown that specific sncRNAs have differential expression between AD patients and cognitively healthy participants [ 17 – 21 ], and some of them exhibit good predictive accuracy [ 22 ]. Furthermore, differential expression of sncRNAs has been observed between individuals with MCI and healthy participants [ 19 , 23 , 24 ].…”

Effects of a High-Fat Diet on Insulin-Related miRNAs in Plasma and Brain Tissue in APPSwe/PS1dE9 and Wild-Type C57BL/6J Mice

“…Among the different types of dementia, Alzheimer's disease (AD) and vascular dementia (VaD) stand out as the most prevalent [3]. Obesity entails several detrimental consequences in the brain, including impaired synaptic plasticity, reduced brain volume, low-grade inflammation and Nutrients 2024, 16, 955 2 of 14 neurodegeneration, that can contribute to AD and other types of dementia [4]. Obesity, but especially central obesity, is commonly found in patients with T2D and it is closely associated with insulin resistance (IR) in peripheral tissues [5].…”

“…Others, such as miR-125b-5p and miR-20b-5p, found in high levels in the hippocampus, were associated with memory impairment [14,15]. Several miRNA signatures, discriminating AD dementia patients from individuals without AD dementia or predicting the conversion in patients from mild-cognitive impairment to AD dementia with high accuracy, were described [16,17]. miRNAs, including miR-29a-3p, miR-34a, miR-125b-5p and miR-20b-5p, within others, have been also related to insulin secretion, beta cell development and the regulation of the insulin signaling pathway [18][19][20][21].…”

Circulating long noncodingRNAs in Mild Cognitive Impairment patients’ blood

“…Again, some miRNAs families as miR-132 and/or miR-134 were shown to be deregulated in MCI patients, speci cally miR-132 for its involvement in tau metabolism through IT PKB gene (Inositol-Trisphosphate 3-Kinase B) targeting [7]. LncRNAs are mRNA-like transcripts (200 nt to > 100 kb), with a biogenesis process similar to mRNAs, but different from them for the lack of an open reading frame (ORF) of signi cant length and the absence of a translation capacity [8].…”