ArticleBrain pathology (Zurich, Switzerland)2022
The association between neurodegeneration and local complement activation in the thalamus to progressive multiple sclerosis outcome.
Article in Brain pathology (Zurich, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 29 citations in OpenAlex.
- The effect of ibudilast on thalamic volume in progressive multiple sclerosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2023Trial
- Shedding Light on Interaction Between Neurological Symptoms and Psychiatric Episodes in Multiple Sclerosis: Novel Hypothesis and Therapeutic Avenues.Molecular neurobiology · 2026Review
- Transcriptome analysis of the prefrontal cortex identifies inflammatory genes associated with cognitive impairment in a model of multiple sclerosis.Cell death discovery · 2026Article
- Characteristic patterns of complement deposition in NMOSD, MOGAD, and MS.Acta neuropathologica · 2026Article
- Subcortical microglial inflammation is uniquely linked to subpial cortical demyelination in multiple sclerosis.NeuroImage. Clinical · 2026Article
- Complement dysregulation in human tauopathies.Brain pathology (Zurich, Switzerland) · 2025Article
- Sterol imbalances and cholesterol-24-hydroxylase dysregulation is linked to the underlying progression of multiple sclerosis.Brain pathology (Zurich, Switzerland) · 2025Article
- Neuropathological and cerebrospinal fluid correlates of choroid plexus inflammation in progressive multiple sclerosis.Brain pathology (Zurich, Switzerland) · 2025Article
- Thalamic atrophy in multiple sclerosis is associated with tract disconnection and altered microglia.Acta neuropathologica · 2025Article
- Aberrant Complement Activation Is Associated With Structural Brain Damage in Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2025Article
- Increased periventricular thalamic damage gradient in multiple sclerosis detected by quantitative gradient echo MRI.Multiple sclerosis and related disorders · 2024Article
- Immunoglobulin G and Complement as Major Players in the Neurodegeneration of Multiple Sclerosis.Biomolecules · 2024Review
- Article
- The complement system in neurodegenerative diseases.Clinical science (London, England : 1979) · 2024Article
- Complement Activation Is Associated With Disease Severity in Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2024Article
- The complement system in neurodegenerative and inflammatory diseases of the central nervous system.Frontiers in neurology · 2024Review
- Meningeal inflammation as a driver of cortical grey matter pathology and clinical progression in multiple sclerosis.Nature reviews. Neurology · 2023Review
- Multiple sclerosis plasma IgG aggregates induce complement-dependent neuronal apoptosis.Cell death & disease · 2023Article
- C1q and central nervous system disorders.Frontiers in immunology · 2023Review
- Cerebrospinal fluid proteomics in recent-onset Narcolepsy type 1 reveals activation of the complement system.Frontiers in immunology · 2023Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
The extent of grey matter demyelination and neurodegeneration in the progressive multiple sclerosis (PMS) brains at post-mortem associates with more severe disease. Regional tissue atrophy, especially affecting the cortical and deep grey matter, including the thalamus, is prognostic for poor outcomes. Microglial and complement activation are important in the pathogenesis and contribute to damaging processes that underlie tissue atrophy in PMS. We investigated the extent of pathology and innate immune activation in the thalamus in comparison to cortical grey and white matter in blocks from 21 cases of PMS and 10 matched controls. Using a digital pathology workflow, we show that the thalamus is invariably affected by demyelination and had a far higher proportion of active inflammatory lesions than forebrain cortical tissue blocks from the same cases. Lesions were larger and more frequent in the medial nuclei near the ventricular margin, whilst neuronal loss was greatest in the lateral thalamic nuclei. The extent of thalamic neuron loss was not associated with thalamic demyelination but correlated with the burden of white matter pathology in other forebrain areas (Spearman r = 0.79, p < 0.0001). Only thalamic neuronal loss, and not that seen in other forebrain cortical areas, correlated with disease duration (Spearman r = -0.58, p = 0.009) and age of death (Spearman r = -0.47, p = 0.045). Immunoreactivity for the complement pattern recognition molecule C1q, and products of complement activation (C4d, Bb and C3b) were elevated in thalamic lesions with an active inflammatory pathology. Complement regulatory protein, C1 inhibitor, was unchanged in expression. We conclude that active inflammatory demyelination, neuronal loss and local complement synthesis and activation in the thalamus, are important to the pathological and clinical disease outcomes of PMS.
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