Abstract
Small extracellular vesicles (EVs) are able to pass from the central nervous system (CNS) into peripheral blood and contain molecule markers of their parental origin. The aim of our study was to isolate and characterize total and neural-derived small EVs (NDEVs) and their micro RNA (miRNA) cargo in Alzheimer’s disease (AD) patients. Small NDEVs were isolated from plasma in a population consisting of 40 AD patients and 40 healthy subjects (CTRLs) using high throughput Advanced TaqMan miRNA OpenArrays®, which enables the simultaneous determination of 754 miRNAs. MiR-23a-3p, miR-223-3p, miR-100-3p and miR-190-5p showed a significant dysregulation in small NDEVs from AD patients as compared with controls (1.16 ± 0.49 versus 7.54 ± 2.5, p = 0.026; 9.32 ± 2.27 versus 0.66 ± 0.18, p <0.0001; 0.069 ± 0.01 versus 0.5 ± 0.1, p < 0.0001 and 2.9 ± 1.2 versus 1.93 ± 0.9, p < 0.05, respectively). A further validation analysis confirmed that miR-23a-3p, miR-223-3p and miR-190a-5p levels in small NDEVs from AD patients were significantly upregulated as compared with controls (p = 0.008; p = 0.016; p = 0.003, respectively) whereas miR-100-3p levels were significantly downregulated (p = 0.008). This is the first study that carries out the comparison between total plasma small EV population and NDEVs, demonstrating the presence of a specific AD NDEV miRNA signature.
Highlights
Alzheimer’s disease (AD) is a chronic neurodegenerative disorder characterized by cognitive decline and memory impairment
Comparisons of ncRNAs levels, expressed by relative quantification (RQ), between patients and controls were performed by using the nonparametric Mann−Whitney test and the correction for multiple comparisons was performed using the post hoc Dunn’s test
The study was structured as follows: (1) discovery phase involving 20 AD patients and 20 CTRLs tested for 754 candidate micro RNA (miRNA) and (2) validation phase, involving the remaining 20 AD samples and 20 controls, for the validation of previously determined best hits miRNAs
Summary
Alzheimer’s disease (AD) is a chronic neurodegenerative disorder characterized by cognitive decline and memory impairment. Increasing epidemiological evidence shows that there is a presymptomatic long-lasting period for clinical incubation of the disease that could take several years before leading to cognitive dysfunction. Diagnostic research criteria for AD [2] include emission tomography (PET) with amyloid tracer, which is a complex and very expensive tool, and the cerebrospinal fluid (CSF) pathogenic protein detection, that implies the invasive procedure of sample collection by lumbar puncture. In this scenario, circulating biomarkers would be of help for differential diagnosis and possibly for monitoring cognitive decline
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
