TY - JOUR
T1 - Mitochondrial measures in neuronally enriched extracellular vesicles predict brain and retinal atrophy in multiple sclerosis
AU - Ladakis, Dimitrios C.
AU - Yao, Pamela J.
AU - Vreones, Michael
AU - Blommer, Joseph
AU - Kalaitzidis, Grigorios
AU - Sotirchos, Elias S.
AU - Fitzgerald, Kathryn C.
AU - Saidha, Shiv
AU - Calabresi, Peter A.
AU - Kapogiannis, Dimitrios
AU - Bhargava, Pavan
N1 - Publisher Copyright:
© The Author(s), 2022.
PY - 2022/11
Y1 - 2022/11
N2 - 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.
AB - 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.
KW - Extracellular vesicles
KW - biomarkers
KW - mitochondrial complexes
KW - multiple sclerosis
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U2 - 10.1177/13524585221106290
DO - 10.1177/13524585221106290
M3 - Article
C2 - 35787218
AN - SCOPUS:85133629878
SN - 1352-4585
VL - 28
SP - 2020
EP - 2026
JO - Multiple Sclerosis Journal
JF - Multiple Sclerosis Journal
IS - 13
ER -