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MiRNA-501-3p and MiRNA-502-3p: A promising biomarker panel for Alzheimer's disease
Davin Devara1, Bhupender Sharma1, Gunjan Goyal1
1Center of Emphasis in Neuroscience, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, Texas, USA.
Introduction:
Alzheimer's disease (AD) lacks a less invasive and early detectable biomarker. Here, we investigated the biomarker potential of miR-501-3p and miR-502-3p using different AD sources.
Methods:
MiR-501-3p and miR-502-3p expressions were evaluated in AD cerebrospinal fluid (CSF) exosomes, serum exosomes, familial and sporadic AD fibroblasts and B-lymphocytes by qRT-PCR analysis. Further, miR-501-3p and miR-502-3p expressions were analysed in APP, Tau plasmid transfected cells media exosomes and in different brain cell types.
Results:
MiR-501-3p and miR-502-3p expressions were significantly up-regulated in AD CSF exosomes relative to controls. MiRNA levels were high in accordance with amyloid plaque and NFT density in multiple brain regions. Similarly, both miRNAs were elevated in AD and MCI serum exosomes compared with controls. MiR-502-3p expression was high in familial AD and sporadic AD B-lymphocytes. MiR-501-3p and miR-502-3p expression were elevated intracellularly and secreted extracellularly in response to APP and Tau pathology. Finally, neurons and astrocytes displayed high expression of these miRNAs.
Discussion:
These results suggest that miR-501-3p and miR-502-3p could be promising biomarkers for AD.
Key Points:
MiR-501-3p and miR-502-3p expression is elevated in AD CSF exosomes, AD serum exosomes, AD B-lymphocytes and Aβ- and Tau-treated cells. MiR-501-3p and miR-502-3p are correlated with amyloid plaque and NFT tangle density in specific brain regions. MiR-501-3p and miR-502-3p are highly expressed in neurons and astrocytes, suggesting that these cells are the source of miRNA secretion. MiR-501-3p and miR-502-3p could be a promising biomarker panel for AD.
Insights
New Alzheimer's disease biomarkers, miR-501-3p and miR-502-3p, show elevated levels in cerebrospinal fluid and serum exosomes. These microRNAs are promising for early AD detection and correlate with disease pathology.
Area of Science:
- Neuroscience
- Molecular Biology
- Biomarker Discovery
Background:
- Alzheimer's disease (AD) diagnosis lacks minimally invasive and early detection biomarkers.
- Investigating novel microRNAs (miRNAs) for their diagnostic potential in AD is crucial.
Purpose of the Study:
- To evaluate the biomarker potential of miR-501-3p and miR-502-3p in various Alzheimer's disease (AD) sources.
- To determine if miR-501-3p and miR-502-3p levels correlate with AD pathology.
Main Methods:
- Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to measure miR-501-3p and miR-502-3p expression.
- Expression levels were analyzed in cerebrospinal fluid (CSF) exosomes, serum exosomes, fibroblasts, and B-lymphocytes from AD patients and controls.
- MiRNA expression was also assessed in cells transfected with APP and Tau plasmids and in different brain cell types.
Main Results:
- MiR-501-3p and miR-502-3p were significantly upregulated in AD CSF exosomes and serum exosomes compared to controls.
- Elevated miRNA levels correlated with amyloid plaque and neurofibrillary tangle (NFT) density in brain regions.
- Both miRNAs were also found to be elevated in familial and sporadic AD B-lymphocytes and in response to amyloid-beta (Aβ) and Tau pathology.
Conclusions:
- MiR-501-3p and miR-502-3p show promise as novel, less invasive biomarkers for Alzheimer's disease (AD).
- These miRNAs are elevated in easily accessible biofluids (CSF and serum) and correlate with key AD pathological hallmarks.
- Neurons and astrocytes are identified as potential sources of these secreted miRNAs in AD.
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