ArticleThe journal of pathology. Clinical research2023
pTDP-43 aggregates accumulate in non-central nervous system tissues prior to symptom onset in amyotrophic lateral sclerosis: a case series linking archival surgical biopsies with clinical phenotypic data.
Article in The journal of pathology. Clinical research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 24 citations in OpenAlex.
- Review
- Peripheral TDP-43 pathology in amyotrophic lateral sclerosis: toward a systemic proteinopathy.Acta neuropathologica · 2026Review
- TDP-43 proteinopathy as a biomarker and therapeutic target in amyotrophic lateral sclerosis.Biochemical Society transactions · 2026Review
- Exploratory assessment of phosphorylated TDP-43 immunoreactivity in minor salivary glands of patients with ALS.Acta neuropathologica communications · 2026Article
- Review
- 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
- Brain Iron as a Surrogate Biomarker of Pathological TDP-43 Identifies Brain Region-Specific Signatures in Ageing, Alzheimer's Disease and Amyotrophic Lateral Sclerosis.bioRxiv : the preprint server for biology · 2025Article
- Integrative genomics and functional immunology reveal Clostridia species as modulators of neuroinflammation in amyotrophic lateral sclerosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 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
- Consensus statement on exploring the Nexus between nutrition, brain health and dementia prevention.Nutrition & metabolism · 2025Review
- Extracellular vesicles in TDP-43 proteinopathies: pathogenesis and biomarker potential.Molecular neurodegeneration · 2025Review
- RNA-binding proteins in ALS and FTD: from pathogenic mechanisms to therapeutic insights.Molecular neurodegeneration · 2025Review
- ALS plasma biomarkers reveal neurofilament and pTau correlate with disease onset and progression.Annals of clinical and translational neurology · 2025Article
- Gut microbiota immune cross-talk in amyotrophic lateral sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Nanoplastics and Neurodegeneration in ALS.Brain sciences · 2024Review
- Excessive nucleic acid R-loops induce mitochondria-dependent epithelial cell necroptosis and drive spontaneous intestinal inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Harnessing the Power of Enteric Glial Cells' Plasticity and Multipotency for Advancing Regenerative Medicine.International journal of molecular sciences · 2023Review
- The Serotonergic System and Amyotrophic Lateral Sclerosis: A Review of Current Evidence.Cellular and molecular neurobiology · 2023Review
- Role of Oxidative Stress on the Etiology and Pathophysiology of Amyotrophic Lateral Sclerosis (ALS) and Its Relation with the Enteric Nervous System.Current issues in molecular biology · 2023Review
- The era of cryptic exons: implications for ALS-FTD.Molecular neurodegeneration · 2023Review
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) are traditionally considered strictly neurological disorders. However, clinical presentation is not restricted to neurological systems, and non-central nervous system (CNS) manifestations, particularly gastrointestinal (GI) symptoms, are common. Our objective was to understand the systemic distribution of pathology in archived non-CNS tissues, taken as part of routine clinical practice during life from people with ALS. We examined tissue from 13 people who went on to develop ALS; including sporadic ALS (n = 12) and C9orf72 hexanucleotide repeat expansion (n = 1). The tissue cohort consisted of 68 formalin-fixed paraffin embedded samples from 21 surgical cases (some patients having more than one case over their lifetimes), from 8 organ systems, which we examined for evidence of phosphorylated TDP-43 (pTDP-43) pathology. We identified pTDP-43 aggregates in multiple cell types of the GI tract, including macrophages and dendritic cells within the lamina propria; as well as ganglion/neuronal and glial cells of the myenteric plexus. Aggregates were also noted within lymph node parenchyma, blood vessel endothelial cells, and chondrocytes. We note that in all cases with non-CNS pTDP-43 pathology, aggregates were present prior to ALS diagnosis and in some instances preceded neurological symptom onset by more than 10 years. These data imply that patients with microscopically unexplained non-CNS symptoms could have occult protein aggregation that could be detected many years prior to neurological involvement.
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