ArticleActa neuropathologica communications2020
Quantitative patterns of motor cortex proteinopathy across ALS genotypes.
Article in Acta neuropathologica communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 52 citations in OpenAlex.
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- Somatic mosaicism in ALS and FTD identifies focal mutations associated with widespread degeneration.Nature genetics · 2026Article
- Statins and genetic inhibition of the mevalonate pathway activate an ATF3-STMN2 regenerative program.bioRxiv : the preprint server for biology · 2026Article
- Blocking RAN translation without altering repeat RNAs rescuesScience (New York, N.Y.) · 2026Article
- Autophagy Dysfunction and Neurodegeneration: Where Does It Go Wrong?Journal of molecular biology · 2025Review
- Challenges of modelling TDP-43 pathology in mice.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Amyotrophic lateral sclerosis caused by TARDBP mutations: from genetics to TDP-43 proteinopathy.The Lancet. Neurology · 2025Review
- Amyotrophic lateral sclerosis represents corticomotoneuronal system failure.Muscle & nerve · 2025Review
- Neuronal TDP-43 aggregation drives changes in microglial morphology prior to immunophenotype in amyotrophic lateral sclerosis.Acta neuropathologica communications · 2025Article
- Comprehending Alzheimer's Disease: Molecular Mechanisms and Treatment Strategies.Current Alzheimer research · 2025Review
- Detection of pTDP-43 via routine muscle biopsy: A promising diagnostic biomarker for amyotrophic lateral sclerosis.Brain pathology (Zurich, Switzerland) · 2024Article
- Review
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- Betz cells of the primary motor cortex.The Journal of comparative neurology · 2024Review
- Heterogeneity of cortical pTDP-43 inclusion morphologies in amyotrophic lateral sclerosis.Acta neuropathologica communications · 2023Article
- TDP-43 differentially propagates to induce antero- and retrograde degeneration in the corticospinal circuits in mouse focal ALS models.Acta neuropathologica · 2023Article
- Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Divergent single cell transcriptome and epigenome alterations in ALS and FTD patients with C9orf72 mutation.Nature communications · 2023Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Degeneration of the primary motor cortex is a defining feature of amyotrophic lateral sclerosis (ALS), which is associated with the accumulation of microscopic protein aggregates in neurons and glia. However, little is known about the quantitative burden and pattern of motor cortex proteinopathies across ALS genotypes. We combined quantitative digital image analysis with multi-level generalized linear modelling in an independent cohort of 82 ALS cases to explore the relationship between genotype, total proteinopathy load and cellular vulnerability to aggregate formation. Primary motor cortex phosphorylated (p)TDP-43 burden and microglial activation were more severe in sporadic ALS-TDP disease than C9-ALS. Oligodendroglial pTDP-43 pathology was a defining feature of ALS-TDP in sporadic ALS, C9-ALS and ALS with OPTN, HNRNPA1 or TARDBP mutations. ALS-FUS and ALS-SOD1 showed less cortical proteinopathy in relation to spinal cord pathology than ALS-TDP, where pathology was more evenly spread across the motor cortex-spinal cord axis. Neuronal pTDP-43 aggregates were rare in GAD67+ and Parvalbumin+ inhibitory interneurons, consistent with predominant accumulation in excitatory neurons. Finally, we show that cortical microglia, but not astrocytes, contain pTDP-43. Our findings suggest divergent quantitative, genotype-specific vulnerability of the ALS primary motor cortex to proteinopathies, which may have implications for our understanding of disease pathogenesis and the development of genotype-specific therapies.
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