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Harnessing the Power of MicroRNA Cargoes in Small Extracellular Vesicles Released from Fresh-Frozen Human Brain Sections
Published on: November 8, 2024
miR-150-5p and let-7b-5p in Blood Myeloid Extracellular Vesicles Track Cognitive Symptoms in Patients with Multiple
Federica Scaroni1, Caterina Visconte2,3, Maria Serpente3,4
1Institute of Neuroscience, CNR, Via Follereau 3, 20854 Vedano al Lambro, Italy.
Abstract:
Cognitive deficits strongly affect the quality of life of patients with multiple sclerosis (MS). However, no cognitive MS biomarkers are currently available. Extracellular vesicles (EVs) contain markers of parental cells and are able to pass from the brain into blood, representing a source of disease biomarkers. The aim of this study was to investigate whether small non-coding microRNAs (miRNAs) targeting synaptic genes and packaged in plasma EVs may reflect cognitive deficits in MS patients. Total EVs were precipitated by Exoquick from the plasma of twenty-six cognitively preserved (CP) and twenty-three cognitively impaired (CI) MS patients belonging to two independent cohorts. Myeloid EVs were extracted by affinity capture from total EVs using Isolectin B4 (IB4). Fourteen miRNAs targeting synaptic genes were selected and measured by RT-PCR in both total and myeloid EVs. Myeloid EVs from CI patients expressed higher levels of miR-150-5p and lower levels of let-7b-5p compared to CP patients. Stratification for progressive MS (PMS) and relapsing-remitting MS (RRMS) and correlation with clinical parameters suggested that these alterations might be attributable to cognitive deficits rather than disease progression. This study identifies miR-150-5p and let-7b-5p packaged in blood myeloid EVs as possible biomarkers for cognitive deficits in MS.
Insights
New research suggests specific microRNAs (miRNAs) within blood extracellular vesicles (EVs) could serve as biomarkers for cognitive impairment in multiple sclerosis (MS) patients. These findings offer hope for improved diagnosis and management of cognitive deficits in MS.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Molecular Biology
Background:
- Cognitive deficits significantly impact multiple sclerosis (MS) patient quality of life.
- Currently, no validated biomarkers exist for cognitive impairment in MS.
- Extracellular vesicles (EVs) in blood may contain brain-derived biomarkers.
Purpose of the Study:
- To investigate if plasma extracellular vesicle (EV)-packaged microRNAs (miRNAs) targeting synaptic genes correlate with cognitive deficits in MS patients.
- To identify potential blood-based biomarkers for cognitive impairment in multiple sclerosis.
Main Methods:
- Plasma extracellular vesicles (EVs) were isolated from cognitively preserved (CP) and cognitively impaired (CI) MS patients.
- Myeloid EVs were specifically extracted using Isolectin B4 (IB4) affinity capture.
- Levels of 14 synaptic gene-targeting miRNAs were measured using RT-PCR in total and myeloid EVs.
Main Results:
- Myeloid EVs from CI MS patients showed elevated miR-150-5p and reduced let-7b-5p compared to CP patients.
- Alterations in these miRNAs were linked to cognitive deficits, independent of MS disease progression (PMS vs. RRMS).
Conclusions:
- miR-150-5p and let-7b-5p within blood myeloid EVs are potential biomarkers for cognitive deficits in multiple sclerosis.
- This discovery could pave the way for non-invasive diagnostic tools for MS-related cognitive impairment.
