ArticleActa neuropathologica communications2018
Phosphorylated TDP-43 (pTDP-43) aggregates in the axial skeletal muscle of patients with sporadic and familial amyotrophic lateral sclerosis.
Article in Acta neuropathologica communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 97 citations in OpenAlex.
- Peripheral TDP-43 pathology in amyotrophic lateral sclerosis: toward a systemic proteinopathy.Acta neuropathologica · 2026Review
- Review of the Pathology of Muscle in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2026Review
- Exploratory assessment of phosphorylated TDP-43 immunoreactivity in minor salivary glands of patients with ALS.Acta neuropathologica communications · 2026Article
- Beyond motor neurons: peripheral TDP-43 pathology in skeletal muscle and intramuscular nerves in amyotrophic lateral sclerosis.Brain communications · 2026Review
- Skin TDP-43 pathology as a candidate biomarker for predicting amyotrophic lateral sclerosis decades prior to motor symptom onset.bioRxiv : the preprint server for biology · 2025Article
- ALS Patients Exhibit Altered Levels of Total and Active MMP-9 and Several Other Biomarkers in Serum and CSF Compared to Healthy Controls and Other Neurologic Diseases.International journal of molecular sciences · 2025Article
- Article
- Peripheral proteinopathy in neurodegenerative diseases.Translational neurodegeneration · 2025Review
- TDP-43-mediated amyotrophic lateral sclerosis: new/hidden insights fromFrontiers in cell and developmental biology · 2025Article
- An overlap-weighted analysis on the association of constipation symptoms with disease progression and survival in amyotrophic lateral sclerosis: a nested case-control study.Therapeutic advances in neurological disorders · 2025Article
- Potential role of stress granules and myogranules in amyotrophic lateral sclerosis.Frontiers in molecular neuroscience · 2025Review
- Seeding-competent TDP-43 persists in human patient and mouse muscle.Science translational medicine · 2024Article
- Detection of pTDP-43 via routine muscle biopsy: A promising diagnostic biomarker for amyotrophic lateral sclerosis.Brain pathology (Zurich, Switzerland) · 2024Article
- Misfolding and aggregation in neurodegenerative diseases: protein quality control machinery as potential therapeutic clearance pathways.Cell communication and signaling : CCS · 2024Review
- In vivo diagnosis of TDP-43 proteinopathies: in search of biomarkers of clinical use.Translational neurodegeneration · 2024Review
- The new missense G376V-TDP-43 variant induces late-onset distal myopathy but not amyotrophic lateral sclerosis.Brain : a journal of neurology · 2024Article
- Muscle Involvement in Amyotrophic Lateral Sclerosis: Understanding the Pathogenesis and Advancing Therapeutics.Biomolecules · 2023Review
- Relation of Motor Impairments to Neuropathologic Changes of Limbic-Predominant Age-Related TDP-43 Encephalopathy in Older Adults.Neurology · 2023Article
- A novel protocol to derive cervical motor neurons from induced pluripotent stem cells for amyotrophic lateral sclerosis.Stem cell reports · 2023Article
- Limbic-predominant age-related TDP43 encephalopathy (LATE) neuropathological change in neurodegenerative diseases.Nature reviews. Neurology · 2023Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Muscle atrophy with weakness is a core feature of amyotrophic lateral sclerosis (ALS) that has long been attributed to motor neuron loss alone. However, several studies in ALS patients, and more so in animal models, have challenged this assumption with the latter providing direct evidence that muscle can play an active role in the disease. Here, we examined the possible role of cell autonomous pathology in 148 skeletal muscle samples from 57 ALS patients, identifying phosphorylated TAR DNA-binding protein (pTDP-43) inclusions in the muscle fibers of 19 patients (33.3%) and 24 tissue samples (16.2% of specimens). A muscle group-specific difference was identified with pTDP-43 pathology being significantly more common in axial (paraspinous, diaphragm) than appendicular muscles (P = 0.0087). This pathology was not significantly associated with pertinent clinical, genetic (c9ALS) or nervous system pathologic data, suggesting it is not limited to any particular subgroup of ALS patients. Among 25 non-ALS muscle samples, pTDP-43 inclusions were seen only in the autophagy-related disorder inclusion body myositis (IBM) (n = 4), where they were more diffuse than in positive ALS samples (P = 0.007). As in IBM samples, pTDP-43 aggregates in ALS were p62/ sequestosome-1-positive, potentially indicating induction of autophagy. Phospho-TDP-43-positive ALS and IBM samples also showed significant up-regulation of TARDBP and SQSTM1 expression. These findings implicate axial skeletal muscle as an additional site of pTDP-43 pathology in some ALS patients, including sporadic and familial cases, which is deserving of further investigation.
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