MicroRNA expression in extracellular vesicles as a novel blood-based biomarker for Alzheimer's disease

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

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By analyzing microRNAs in small extracellular vesicles in the blood, unique cellular and molecular information related to the onset and progression of Alzheimer's disease can be obtained. The study found that specific microRNAs in certain subtypes of small extracellular vesicles showed differential expression in individuals with normal cognition, mild cognitive impairment, MCI conversion to AD dementia, and AD dementia, and were correlated with cortical thickness on magnetic resonance imaging. These findings suggest that microRNA analysis in specific extracellular vesicles may serve as a novel blood-based molecular biomarker for Alzheimer's disease.