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Updated: Aug 22, 2025

Harnessing the Power of MicroRNA Cargoes in Small Extracellular Vesicles Released from Fresh-Frozen Human Brain Sections
Published on: November 8, 2024
Circulating extracellular vesicle-containing microRNAs reveal potential pathogenesis of Alzheimer's disease
Yi Wang1, Ping Yuan2, Lu Ding3
1Translational Research Center, Shanghai Yangzhi Rehabilitation Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.
Abstract:
The pathogenesis of Alzheimer's disease (AD) remains unknown till today, hindering the research and development of AD therapeutics and diagnostics. Circulating extracellular vesicles (EVs) can be utilized as a new window to spy upon AD pathogenesis. Altered microRNA profiles were noted in both the cerebrospinal fluid (CSF)- and blood-isolated EVs of AD patients, implying the outstanding potential of circulating EV-containing miRNAs (CEmiRs) to serve as important regulators in AD pathogenesis. Although several CEmiRs were found to play a part in AD, the association of globally altered miRNA profiles in patients' serum-derived EVs with AD pathogenesis remains unclear. In this study, we first investigated the miRNA profile in serum-derived EVs from AD, mild cognitive impairment (MCI) patients, and healthy individuals. We observed differential expression patterns of CEmiRs and classified them into 10 clusters. We identified the predicted targets of these differentially expressed CEmiRs (DECEmiRs) and analyzed their biological functions and interactions. Our study revealed the temporal regulation of complex and precise signaling networks on AD pathogenesis, shedding light on the development of novel therapeutic strategies, including multi-target drug combination for AD treatment.
Insights
Researchers explored microRNA profiles in extracellular vesicles (EVs) from Alzheimer's disease (AD) patients. This study reveals key circulating EV-containing miRNAs (CEmiRs) linked to AD pathogenesis, offering new therapeutic targets.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Alzheimer's disease (AD) pathogenesis remains largely unknown, impeding therapeutic and diagnostic advancements.
- Circulating extracellular vesicles (EVs) offer a promising avenue for understanding AD.
- Altered microRNA (miRNA) profiles in EVs from AD patients suggest their role in disease.
Purpose of the Study:
- To investigate the global miRNA profile in serum-derived EVs from AD, mild cognitive impairment (MCI), and healthy individuals.
- To identify differentially expressed CEmiRs (DECEmiRs) and their potential targets in AD.
- To elucidate the role of CEmiRs in AD pathogenesis and signaling networks.
Main Methods:
- Serum-derived EVs were isolated from AD, MCI, and healthy control groups.
- Comprehensive miRNA profiling of serum-derived EVs was performed.
- Bioinformatic analysis was used to identify DECEmiRs, predict targets, and analyze biological functions and interactions.
Main Results:
- Distinct miRNA expression patterns were observed in serum-derived EVs across AD, MCI, and healthy groups, classified into 10 clusters.
- Identification of specific DECEmiRs implicated in AD pathogenesis.
- Elucidation of complex signaling networks regulated by CEmiRs in AD.
Conclusions:
- Circulating EV-miRNAs represent crucial regulators in Alzheimer's disease pathogenesis.
- The study provides insights into temporal regulation of signaling networks in AD.
- Findings support the development of novel therapeutic strategies, including multi-target drug combinations for AD.
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