ArticleAnnals of neurology2021
Iron Heterogeneity in Early Active Multiple Sclerosis Lesions.
Article in Annals of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Polydatin and Nicotinamide Prevent Iron Accumulation and Lipid Peroxidation in Cellular Models of Mitochondrial Diseases.Antioxidants (Basel, Switzerland) · 2025Article
- A Window into New Insights on Progression Independent of Relapse Activity in Multiple Sclerosis: Role of Therapies and Current Perspective.International journal of molecular sciences · 2025Review
- Article
- Drosophila Evi5 is a critical regulator of intracellular iron transport via transferrin and ferritin interactions.Nature communications · 2024Article
- Transcript Profiles of Microglia/Macrophage Cells at the Borders of Chronic Active and Subpial Gray Matter Lesions in Multiple Sclerosis.Annals of neurology · 2024Article
- Cell-binding IgM in CSF is distinctive of multiple sclerosis and targets the iron transporter SCARA5.Brain : a journal of neurology · 2024Article
- Tumefactive Demyelination in MOG Ab-Associated Disease, Multiple Sclerosis, and AQP-4-IgG-Positive Neuromyelitis Optica Spectrum Disorder.Neurology · 2023Article
- Glia Connect Inflammation and Neurodegeneration in Multiple Sclerosis.Neuroscience bulletin · 2023Review
- Biomolecular alterations detected in multiple sclerosis skin fibroblasts using Fourier transform infrared spectroscopy.Frontiers in cellular neuroscience · 2023Article
- A New Advanced MRI Biomarker for Remyelinated Lesions in Multiple Sclerosis.Annals of neurology · 2022Article
- X-ray fluorescence microscopy methods for biological tissues.Metallomics : integrated biometal science · 2022Review
- Opportunities for Molecular Imaging in Multiple Sclerosis Management: Linking Probe to Treatment.Radiology · 2022Review
- Cerebral Iron Deposition in Neurodegeneration.Biomolecules · 2022Review
- The role of glial cells in multiple sclerosis disease progression.Nature reviews. Neurology · 2022Review
- Iron deposition heterogeneity in extrapyramidal system assessed by quantitative susceptibility mapping in Parkinson's disease patients with type 2 diabetes mellitus.Frontiers in aging neuroscience · 2022Article
- Identification of Novel Key Genes and Pathways in Multiple Sclerosis Based on Weighted Gene Coexpression Network Analysis and Long Noncoding RNA-Associated Competing Endogenous RNA Network.Oxidative medicine and cellular longevity · 2022Article
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- Parkinson's Disease Dementia: Synergistic Effects of Alpha-Synuclein, Tau, Beta-Amyloid, and Iron.Frontiers in aging neuroscience · 2021Article
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Corrections and comments
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Authors and funding
15 authors at 8 institutions in 4 countries.
Funding
Abstract
objectiveMultiple sclerosis (MS) is a heterogeneous inflammatory demyelinating disease. Iron distribution is altered in MS patients' brains, suggesting iron liberation within active lesions amplifies demyelination and neurodegeneration. Whether the amount and distribution of iron are similar or different among different MS immunopatterns is currently unknown.
methodsWe used synchrotron X-ray fluorescence imaging, histology, and immunohistochemistry to compare the iron quantity and distribution between immunopattern II and III early active MS lesions. We analyzed archival autopsy and biopsy tissue from 21 MS patients.
resultsImmunopattern II early active lesions contain 64% more iron (95% confidence interval [CI] = 17-127%, p = 0.004) than immunopattern III lesions, and 30% more iron than the surrounding periplaque white matter (95% CI = 3-64%, p = 0.03). Iron in immunopattern III lesions is 28% lower than in the periplaque white matter (95% CI = -40 to -14%, p < 0.001). When normalizing the iron content of early active lesions to that of surrounding periplaque white matter, the ratio is significantly higher in immunopattern II (p < 0.001). Microfocused X-ray fluorescence imaging shows that iron in immunopattern II lesions localizes to macrophages, whereas macrophages in immunopattern III lesions contain little iron.
interpretationIron distribution and content are heterogeneous in early active MS lesions. Iron accumulates in macrophages in immunopattern II, but not immunopattern III lesions. This heterogeneity in the two most common MS immunopatterns may be explained by different macrophage polarization, origin, or different demyelination mechanisms, and paves the way for developing new or using existing iron-sensitive magnetic resonance imaging techniques to differentiate among immunopatterns in the general nonbiopsied MS patient population. ANN NEUROL 2021;89:498-510.
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