ArticleActa neuropathologica communications2019
Phosphorylated TDP-43 aggregates in skeletal and cardiac muscle are a marker of myogenic degeneration in amyotrophic lateral sclerosis and various conditions.
Article in Acta neuropathologica communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- A molecular systems architecture of neuromuscular junction in amyotrophic lateral sclerosis.NPJ systems biology and applications · 2025Pooled it
- FBXL21 regulates diurnal proteostasis in skeletal muscle by targeting DNAJB6 and client proteins.EMBO reports · 2026Article
- Peripheral TDP-43 pathology in amyotrophic lateral sclerosis: toward a systemic proteinopathy.Acta neuropathologica · 2026Review
- TDP-43 sustains satellite cells to maintain and regenerate skeletal muscle.Stem cell reports · 2026Article
- APOE ε4 influences the widespread TDP-43 pathological subtype in sporadic amyotrophic lateral sclerosis.Acta neuropathologica · 2026Article
- 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
- Surface electrical impedance myography detects disease in an adult-onset SOD1-G93A zebrafish model of amyotrophic lateral sclerosis.Scientific reports · 2025Article
- 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
- SUMO2/3 conjugation of TDP-43 protects against aggregation.Science advances · 2025Article
- Peripheral proteinopathy in neurodegenerative diseases.Translational neurodegeneration · 2025Review
- Gain-of-function ANXA11 mutation cause late-onset ALS with aberrant protein aggregation, neuroinflammation and autophagy impairment.Acta neuropathologica communications · 2025Article
- TDP-43-mediated amyotrophic lateral sclerosis: new/hidden insights fromFrontiers in cell and developmental biology · 2025Article
- Potential role of stress granules and myogranules in amyotrophic lateral sclerosis.Frontiers in molecular neuroscience · 2025Review
- Riluzole is associated with reduced risk of heart failure.European journal of neurology · 2025Article
- 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
- Dysregulated FOXO1 activity drives skeletal muscle intrinsic dysfunction in amyotrophic lateral sclerosis.Acta neuropathologica · 2024Article
- Neurodegenerative disorders, metabolic icebergs, and mitohormesis.Translational neurodegeneration · 2024Review
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAmyotrophic lateral sclerosis (ALS) is characterized pathologically by the occurrence of phosphorylated TDP-43 (pTDP-43)-immunoreactive neuronal and glial inclusions in the central nervous system. Recent studies have shown that pTDP-43 aggregates also occur in the skeletal muscles in a certain proportion of ALS patients.
aimThe aim of this study was to clarify the distribution and incidence of pTDP-43 aggregates in the skeletal and cardiac muscles of patients with ALS, and also those of patients with neuromuscular diseases (NMDs) and non-NMDs. MATERIAL AND
methodsFive regions of muscle (tongue, cervical muscle, diaphragm, iliopsoas muscle and heart) were examined histologically and immunohistochemically in patients with ALS (n = 30), NMDs (n = 13) and non-NMDs (n = 7).
resultsTwo types of pTDP-43 aggregates were distinguishable morphologically: dense filamentous and short linear inclusions. These inclusions were found in at least one of the five muscle regions in all 30 cases of ALS; skeletal muscles in 28 cases and myocardium in 12. pTDP-43 aggregates were also found in 9 of 13 patients with NMDs, including myositis, muscular dystrophy and mitochondrial myopathy, as well as in 3 of 7 patients with non-NMDs. In ALS, pTDP-43 aggregates were most frequent in the diaphragm (19 cases). The mean density of pTDP-43 aggregates in ALS was significantly higher than that in NMDs and non-NMDs. In contiguous sections stained with hematoxylin and eosin and anti-pTDP-43, muscle fibers with dense filamentous inclusions demonstrated single-fiber atrophy with vacuolar degeneration.
conclusionThe present findings indicate that pTDP-43 aggregates in skeletal and cardiac muscle are a myogenic pathological marker in multiple diseases including ALS.
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