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Updated: Sep 5, 2025
Harnessing the Power of MicroRNA Cargoes in Small Extracellular Vesicles Released from Fresh-Frozen Human Brain Sections
Published on: November 8, 2024
Mitochondrial measures in neuronally enriched extracellular vesicles predict brain and retinal atrophy in multiple
Dimitrios C Ladakis1, Pamela J Yao2, Michael Vreones2
1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Background:
Mitochondrial dysfunction plays an important role in multiple sclerosis (MS) disease progression. Plasma extracellular vesicles are a potential source of novel biomarkers in MS, and some of these are derived from mitochondria and contain functional mitochondrial components.
Objective:
To evaluate the relationship between levels of mitochondrial complex IV and V activity in neuronally enriched extracellular vesicles (NEVs) and brain and retinal atrophy as assessed using serial magnetic resonance imaging (MRI) and optical coherence tomography (OCT).
Methods:
Our cohort consisted of 48 people with MS. NEVs were immunocaptured from plasma and mitochondrial complex IV and V activity levels were measured. Subjects underwent OCT every 6 months and brain MRI annually. The associations between baseline mitochondrial complex IV and V activities and brain substructure and retinal thickness changes were estimated utilizing linear mixed-effects models.
Results:
We found that higher mitochondrial complex IV activity and lower mitochondrial complex V activity levels were significantly associated with faster whole-brain volume atrophy. Similar results were found with other brain substructures and retinal layer atrophy.
Conclusion:
Our results suggest that mitochondrial measures in circulating NEVs could serve as potential biomarkers of disease progression and provide the rationale for larger follow-up longitudinal studies.
