miR-132-3p is down-regulated in plasma and CD171+ extracellular vesicles isolated from patients with mild Alzheimer's disease
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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Matilde Sbriscia1, Tatiana Spadoni2, Patrizia Ambrogini3
1Clinic of Laboratory and Precision Medicine, IRCCS INRCA, Ancona, Italy.
Abstract:
Alzheimer's disease (AD), the most prevalent neurodegenerative disorder in aging populations, demands minimally invasive biomarkers for early diagnosis and monitoring. Circulating microRNAs (miRNAs) show promise as such biomarkers. In this study, we examined the levels of five selected miRNAs, implicated in neurodegenerative processes, in plasma and neuron-derived extracellular vesicles (EVs) from cognitively healthy controls (n = 5), and patients with mild (n = 10) and moderate AD (n = 10), stratified by Mini-Mental State Examination (MMSE). miR-23a-3p, miR-223a-3p, and miR-132-3p were significantly downregulated in both plasma and EVs of AD patients, with miR-132-3p emerging as the strongest biomarker candidate for mild AD. Plasma miRNA levels strongly correlated with EV cargo, supporting plasma-based assessments. To validate these findings, miR-132-3p levels were analyzed in expanded cohorts, including cognitively healthy subjects (n = 36), mild AD (n = 37), and moderate AD (n = 40), as well as a cohort of subjects with mild cognitive impairment (MCI, n = 31) and an additional external cohort of cognitively healthy subjects (CTR external, n = 37). Results confirmed miR-132-3p downregulation in AD patients and revealed a significant elevation in MCI individuals, suggesting a potential neuroprotective role in AD early stages. These findings highlight miR-132-3p as a promising, minimally invasive biomarker for early AD diagnosis and disease progression monitoring.
Insights
Circulating microRNAs (miRNAs) like miR-132-3p show promise as Alzheimer's disease (AD) biomarkers. Downregulated in AD patients and elevated in mild cognitive impairment, miR-132-3p aids early diagnosis and monitoring.
Area of Science:
- Neuroscience
- Biochemistry
- Genetics
Background:
- Alzheimer's disease (AD) is a leading cause of neurodegeneration in aging populations.
- Early diagnosis and monitoring of AD require minimally invasive biomarkers.
- Circulating microRNAs (miRNAs) are emerging as potential biomarkers for neurodegenerative disorders.
Purpose of the Study:
- To investigate the levels of selected miRNAs in plasma and extracellular vesicles (EVs) of AD patients and controls.
- To identify potential miRNA biomarkers for early AD diagnosis and disease progression.
- To explore the role of miR-132-3p in mild cognitive impairment (MCI) and AD.
Main Methods:
- Analysis of five selected miRNAs (miR-23a-3p, miR-223a-3p, miR-132-3p) in plasma and neuron-derived EVs from controls, mild AD, and moderate AD patients.
- Stratification of patients by Mini-Mental State Examination (MMSE) scores.
- Validation of miR-132-3p levels in expanded cohorts, including MCI and external control groups.
Main Results:
- miR-23a-3p, miR-223a-3p, and miR-132-3p were significantly downregulated in plasma and EVs of AD patients compared to controls.
- miR-132-3p demonstrated the strongest potential as a biomarker for mild AD.
- Plasma miRNA levels correlated with EV miRNA cargo.
- miR-132-3p was downregulated in AD patients and significantly elevated in MCI individuals.
Conclusions:
- miR-132-3p is a promising minimally invasive biomarker for early AD diagnosis.
- Changes in miR-132-3p levels may indicate disease progression.
- Elevated miR-132-3p in MCI suggests a potential neuroprotective role in early AD stages.
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