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Updated: Aug 2, 2025
Harnessing the Power of MicroRNA Cargoes in Small Extracellular Vesicles Released from Fresh-Frozen Human Brain Sections
Published on: November 8, 2024
MicroRNA expression in extracellular vesicles as a novel blood-based biomarker for Alzheimer's disease
Ashish Kumar1, Yixin Su1, Mitu Sharma1
1Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Introduction:
Brain cell-derived small extracellular vesicles (sEVs) in blood offer unique cellular and molecular information related to the onset and progression of Alzheimer's disease (AD). We simultaneously enriched six specific sEV subtypes from the plasma and analyzed a selected panel of microRNAs (miRNAs) in older adults with/without cognitive impairment.
Methods:
Total sEVs were isolated from the plasma of participants with normal cognition (CN; n = 11), mild cognitive impairment (MCI; n = 11), MCI conversion to AD dementia (MCI-AD; n = 6), and AD dementia (n = 11). Various brain cell-derived sEVs (from neurons, astrocytes, microglia, oligodendrocytes, pericytes, and endothelial cells) were enriched and analyzed for specific miRNAs.
Results:
miRNAs in sEV subtypes differentially expressed in MCI, MCI-AD, and AD dementia compared to the CN group clearly distinguished dementia status, with an area under the curve (AUC) > 0.90 and correlated with the temporal cortical region thickness on magnetic resonance imaging (MRI).
Discussion:
miRNA analyses in specific sEVs could serve as a novel blood-based molecular biomarker for AD.
Highlights:
Multiple brain cell-derived small extracellular vesicles (sEVs) could be isolated simultaneously from blood. MicroRNA (miRNA) expression in sEVs could detect Alzheimer's disease (AD) with high specificity and sensitivity. miRNA expression in sEVs correlated with cortical region thickness on magnetic resonance imaging (MRI). Altered expression of miRNAs in sEVCD31 and sEVPDGFRβ suggested vascular dysfunction. miRNA expression in sEVs could predict the activation state of specific brain cell types.
Insights
Blood-based small extracellular vesicles (sEVs) carrying microRNAs (miRNAs) show promise for Alzheimer's disease (AD) detection. These brain cell-derived sEVs accurately distinguish dementia status and correlate with brain structure changes.
Area of Science:
- Neuroscience
- Biochemistry
- Genetics
Background:
- Alzheimer's disease (AD) diagnosis relies on clinical assessment and costly imaging/fluid biomarkers.
- Small extracellular vesicles (sEVs) derived from brain cells circulate in blood, offering potential insights into neurological conditions.
- Specific microRNAs (miRNAs) within sEVs may reflect brain cell activity and disease states.
Purpose of the Study:
- To investigate the diagnostic potential of miRNAs within specific brain cell-derived sEV subtypes isolated from blood for Alzheimer's disease.
- To correlate miRNA expression in sEVs with cognitive status and brain structure in older adults.
Main Methods:
- Simultaneous enrichment of six brain cell-derived sEV subtypes (neuronal, astrocyte, microglia, oligodendrocyte, pericyte, endothelial) from plasma.
- Analysis of specific miRNA expression profiles within these enriched sEV subtypes.
- Comparison of miRNA expression between cognitively normal individuals and those with mild cognitive impairment (MCI) or AD dementia.
Main Results:
- Differential miRNA expression in sEV subtypes effectively distinguished between normal cognition, MCI, MCI-to-AD conversion, and AD dementia (AUC > 0.90).
- Plasma sEV miRNA levels correlated with temporal cortical thickness measured by MRI.
- Specific miRNA alterations in endothelial and pericyte-derived sEVs suggested vascular dysfunction.
Conclusions:
- Plasma-derived, brain cell-specific sEV miRNAs represent a novel, highly sensitive, and specific blood-based biomarker for Alzheimer's disease.
- sEV miRNA profiles can reflect disease progression and correlate with neuroimaging findings.
- This approach may offer a non-invasive method for early AD detection and monitoring.
