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Plasma-Derived miRNAs as Fluid Biomarkers to Differentiate Alzheimer's and Frontotemporal Dementia
Rosalinda Di Gerlando1,2, Francesca Dragoni2, Evelyne Minucchi2,3
1Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, 27100 Pavia, Italy.
Abstract:
Alzheimer's disease (AD) and Frontotemporal Dementia (FTD) are complex neurodegenerative disorders, often sharing overlapping symptoms. Non-coding RNAs may be involved in pathological processes in these conditions, hence the study of miRNAs isolated from plasma-derived extracellular vesicles (EVs) could provide exploratory insights into the molecular background. The main aim of this work was to identify shared deregulated miRNAs presenting different expression patterns in the two pathologies. A selection of the identified deregulated miRNAs was further studied with the purpose of identifying their mRNA targets and generating hypotheses on their potential pathological involvement. A total of 340 and 291 differentially expressed miRNAs were found in FTD and AD, respectively. Among the commonly deregulated miRNAs with opposite expression patterns between the two conditions, miR-638 emerged as a candidate of interest, showing consistent patterns across our experimental analyses. Nevertheless, these findings are preliminary and intended to be interpreted cautiously, requiring validation in larger cohorts. In addition, the expression of two of its predicted targets in peripheral blood mononuclear cells (PBMCs) appeared to align with miR-638 expression in the same cell type and may reflect potential differences in underlying brain pathological states.
Insights
Researchers identified specific microRNAs (miRNAs) in extracellular vesicles that show different expression patterns in Alzheimer's disease (AD) and Frontotemporal Dementia (FTD). MiR-638 was a key finding, potentially offering insights into these neurodegenerative diseases.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Alzheimer's disease (AD) and Frontotemporal Dementia (FTD) are neurodegenerative disorders with overlapping symptoms.
- Non-coding RNAs, specifically microRNAs (miRNAs), are implicated in neurodegenerative disease pathology.
- Plasma-derived extracellular vesicles (EVs) offer a potential source for identifying disease biomarkers.
Purpose of the Study:
- To identify shared deregulated miRNAs with distinct expression patterns in AD and FTD.
- To investigate potential mRNA targets of identified miRNAs.
- To generate hypotheses regarding the pathological involvement of these miRNAs in AD and FTD.
Main Methods:
- Differential expression analysis of miRNAs in plasma-derived EVs from AD and FTD patients.
- Identification of commonly deregulated miRNAs between AD and FTD.
- Analysis of predicted mRNA targets for selected miRNAs.
- Validation of miRNA and target gene expression in peripheral blood mononuclear cells (PBMCs).
Main Results:
- 340 differentially expressed miRNAs in FTD and 291 in AD were identified.
- miR-638 was identified as a commonly deregulated miRNA with opposite expression patterns in AD and FTD.
- Expression patterns of two predicted miR-638 targets in PBMCs correlated with miR-638 expression, suggesting potential links to brain pathology.
Conclusions:
- The study identified miR-638 as a potential biomarker with differential expression in AD and FTD.
- Preliminary findings suggest miR-638 and its targets may play a role in the distinct pathological processes of AD and FTD.
- Further validation in larger cohorts is necessary to confirm these preliminary findings.
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