4.3 Article

Mitochondrial measures in neuronally enriched extracellular vesicles predict brain and retinal atrophy in multiple sclerosis

期刊

MULTIPLE SCLEROSIS JOURNAL
卷 28, 期 13, 页码 2020-2026

出版社

SAGE PUBLICATIONS LTD
DOI: 10.1177/13524585221106290

关键词

Extracellular vesicles; mitochondrial complexes; multiple sclerosis; biomarkers

资金

  1. Myelin Repair Foundation
  2. EMD Serono Inc., USA, an affiliate of Merck KGaA, Darmstadt, Germany, through MS-LINK
  3. National Institute on Aging, NIH
  4. NIH [1S10OD021648]
  5. National MS Society

向作者/读者索取更多资源

This study aimed to evaluate the relationship between levels of mitochondrial complex IV and V activity and brain and retinal atrophy in multiple sclerosis (MS). The results showed that higher mitochondrial complex IV activity and lower mitochondrial complex V activity levels were significantly associated with faster whole-brain volume atrophy. The findings suggest that mitochondrial measures in circulating extracellular vesicles could serve as potential biomarkers of disease progression in MS.
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.

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