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

Abstract

INTRODUCTIONBrain 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.METHODSTotal 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.RESULTSmiRNAs 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).DISCUSSIONmiRNA 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.

Recognizing Alzheimer's disease from perspective of oligodendrocytes: Phenomena or pathogenesis?

“…In fact, miRNAs play an important role in the development of AD by regulating the survival of neurons, synaptic plasticity, and inflammatory response 143–145 . By contrast, we found that there are only a few research reports on the involvement of miRNAs in the differentiation and maturation of OLs in AD 146,147 . How miRNAs regulate factors of OLs differentiation and maturation in AD is worth further exploration.…”

A Liquid Biopsy-Based Approach to Isolate and Characterize Adipose Tissue-Derived Extracellular Vesicles from Blood

“…Adipose tissue specific sEV were isolated from plasma by immunoprecipitation method as reported by us previously. − , Briefly, 350 μg of total plasma sEV was taken, and the volume was brought to 400 μL with PBS (0.1 μm filtered; Ca 2+ and Mg 2+ free). Two μg of each biotin tagged antibody, CA3 (LS-C687667, LsBio, Seattle, USA), STEAP4 (NB100-68162, Novus Biologicals, Colorado, USA), FABP4 (ARP33794_P050-Biotin, Aviva system biology, California, USA), GGT5 (MBS9207792, Mybiosource, California, USA), and CAMKIIα (NB100-1983B, Novus Biologicals), were added to the total sEV and incubated at 4 °C overnight on hula mixer.…”

“…In the past decade, numerous studies have shown the feasibility of isolating cell/tissue-specific sEV from the biofluids, exploiting the specific markers expressed on the surface using immunoprecipitation methods. Neuron-derived sEV isolated from plasma have been shown to be valuable biomarkers for various neurodegenerative diseases and assessment of responses to treatment. − In recent studies, we have reported the usefulness of brain cells derived sEV from the plasma toward accessing the expression of various neurodegenerative biomarkers , as well as determining the molecular effects of specific dietary intervention against mild-cognitive impairment . Only limited attempts have been made to isolate and characterize adipose tissue-derived sEV (sEV AT ) from plasma.…”

Novel method for collecting hippocampal interstitial fluid extracellular vesicles (EVISF) reveals sex‐dependent changes in microglial EV proteome in response to Aβ pathology

“…Flow cytometry analysis was performed to evaluate the percentage of typical EV tetraspanin markers following methods and controls reported recently (Kumar et al, 2022(Kumar et al, , 2023Mishra et al, 2023)…”