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Updated: May 21, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Clonally expanded mitochondrial DNA deletions within the choroid plexus in multiple sclerosis
Graham R Campbell1, Yevgenya Kraytsberg, Kim J Krishnan
1The Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Abstract:
Mitochondrial DNA deletions (∆-mtDNA) have been implicated in the pathogenesis of Alzheimer's disease (AD), multiple sclerosis (MS) and Parkinson's disease (PD), as well as ageing. Clonal expansion of ∆-mtDNA is the process by which a mutant mtDNA molecule increases to high levels within a single cell containing both wild-type and mutant mtDNA. Unlike in AD and PD, the diffuse inflammatory process in MS involves the choroid plexus, and mitochondria are exposed to reactive oxygen and nitrogen species over a prolonged period. We determined the extent of respiratory enzyme deficiency and ∆-mtDNA at a single cell level within choroid plexus epithelial cells in MS as well as in AD, PD and controls. The respiratory enzyme-deficient (lacking complex IV and with intact complex II activity) cells were more prevalent within the choroid plexus in AD, MS and PD compared with controls. The main catalytic subunit of complex IV (subunit-I of cytochrome c oxidase) was lacking in significantly more respiratory enzyme-deficient cells in MS compared with AD, PD and controls. The single cell analysis showed a fourfold increase in the percentage of respiratory enzyme-deficient choroid plexus epithelial cells harbouring clonally expanded ∆-mtDNA in MS. Our findings establish clonal expansion of ∆-mtDNA as a feature relatively more prominent within the choroid plexus epithelium in MS than AD, PD or controls. We propose clonal expansion of ∆-mtDNA as a molecular link between inflammation and part of a delayed cellular energy failure in MS.
Insights
Mitochondrial DNA deletions (∆-mtDNA) are more prominent in the choroid plexus of multiple sclerosis (MS) patients. This finding links inflammation to cellular energy failure in MS.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Mitochondrial DNA deletions (∆-mtDNA) are linked to neurodegenerative diseases like Alzheimer's (AD), Parkinson's (PD), and multiple sclerosis (MS), as well as aging.
- The choroid plexus, involved in MS inflammation, exposes mitochondria to oxidative stress, potentially promoting ∆-mtDNA accumulation.
- Clonal expansion of ∆-mtDNA signifies a rise in mutant mtDNA within a single cell.
Purpose of the Study:
- To investigate the prevalence of respiratory enzyme deficiency and ∆-mtDNA in choroid plexus epithelial cells across MS, AD, PD, and control groups at a single-cell level.
- To determine if clonal expansion of ∆-mtDNA is a significant feature in the choroid plexus, particularly in MS.
Main Methods:
- Single-cell analysis of choroid plexus epithelial cells.
- Assessment of respiratory enzyme deficiency (specifically Complex IV and Complex II activity).
- Quantification of ∆-mtDNA and its clonal expansion.
Main Results:
- Respiratory enzyme-deficient cells were more common in the choroid plexus of AD, MS, and PD patients compared to controls.
- A significantly higher proportion of these deficient cells in MS lacked the main catalytic subunit of Complex IV (cytochrome c oxidase subunit-I) compared to AD, PD, and controls.
- MS showed a fourfold increase in respiratory enzyme-deficient choroid plexus epithelial cells with clonally expanded ∆-mtDNA.
Conclusions:
- Clonal expansion of ∆-mtDNA is a more prominent feature in the choroid plexus epithelium of MS patients than in AD, PD, or controls.
- This expansion may serve as a molecular link connecting inflammation and delayed cellular energy failure in MS.
- The findings highlight the specific role of the choroid plexus in MS pathogenesis related to mitochondrial dysfunction.
