ArticleActa neuropathologica communications2021
Blood-spinal cord barrier leakage is independent of motor neuron pathology in ALS.
Article in Acta neuropathologica communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 49 citations in OpenAlex.
- Accelerated MCDW-pCASL Using Subspace Low-Rank Reconstruction for Quantification of BBB Water Exchange and Permeability.medRxiv : the preprint server for health sciences · 2026Article
- Cardiovascular ageing: hallmarks, signaling pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Microvascular pathology in the spinal cord of severe spinal muscular atrophy patients.Acta neuropathologica communications · 2026Article
- Microvascular pathology in the spinal cord of severe spinal muscular atrophy patients.Research square · 2025Article
- Review
- Lipid metabolism in microglia: Emerging mechanisms and therapeutic opportunities for neurodegenerative diseases (Review).International journal of molecular medicine · 2025Review
- Restoring brain barriers: an innovative approach for treating neurological disorders.Fluids and barriers of the CNS · 2025Review
- Laminins and the blood-brain barrier.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- Caveolae-Mediated Transcytosis and Its Role in Neurological Disorders.Biomolecules · 2025Review
- Neuronal TDP-43 aggregation drives changes in microglial morphology prior to immunophenotype in amyotrophic lateral sclerosis.Acta neuropathologica communications · 2025Article
- Distribution of ubiquilin 2 and TDP-43 aggregates throughout the CNS in UBQLN2 p.T487I-linked amyotrophic lateral sclerosis and frontotemporal dementia.Brain pathology (Zurich, Switzerland) · 2024Article
- Choroid plexus enlargement in amyotrophic lateral sclerosis patients and its correlation with clinical disability and blood-CSF barrier permeability.Fluids and barriers of the CNS · 2024Article
- Transient Receptor Potential Channels in the Healthy and Diseased Blood-Brain Barrier.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2024Review
- β1 integrins play a critical role maintaining vascular integrity in the hypoxic spinal cord, particularly in white matter.Acta neuropathologica communications · 2024Article
- Interplay between the Glymphatic System and the Endocannabinoid System: Implications for Brain Health and Disease.International journal of molecular sciences · 2023Review
- Brain macrophage development, diversity and dysregulation in health and disease.Cellular & molecular immunology · 2023Review
- Spinal Cord Blood Vessels in Aged Mice Show Greater Levels of Hypoxia-Induced Vascular Disruption and Microglial Activation.International journal of molecular sciences · 2023Article
- Patching Up the Permeability: The Role of Stem Cells in Lessening Neurovascular Damage in Amyotrophic Lateral Sclerosis.Stem cells translational medicine · 2022Review
- Deciphering lipid dysregulation in ALS: from mechanisms to translational medicine.Translational neurodegeneration · 2022Review
- The Cell Autonomous and Non-Cell Autonomous Aspects of Neuronal Vulnerability and Resilience in Amyotrophic Lateral Sclerosis.Biology · 2022Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving progressive degeneration of upper and lower motor neurons. The pattern of lower motor neuron loss along the spinal cord follows the pattern of deposition of phosphorylated TDP-43 aggregates. The blood-spinal cord barrier (BSCB) restricts entry into the spinal cord parenchyma of blood components that can promote motor neuron degeneration, but in ALS there is evidence for barrier breakdown. Here we sought to quantify BSCB breakdown along the spinal cord axis, to determine whether BSCB breakdown displays the same patterning as motor neuron loss and TDP-43 proteinopathy. Cerebrospinal fluid hemoglobin was measured in living ALS patients (n = 87 control, n = 236 ALS) as a potential biomarker of BSCB and blood-brain barrier leakage. Cervical, thoracic, and lumbar post-mortem spinal cord tissue (n = 5 control, n = 13 ALS) were then immunolabelled and semi-automated imaging and analysis performed to quantify hemoglobin leakage, lower motor neuron loss, and phosphorylated TDP-43 inclusion load. Hemoglobin leakage was observed along the whole ALS spinal cord axis and was most severe in the dorsal gray and white matter in the thoracic spinal cord. In contrast, motor neuron loss and TDP-43 proteinopathy were seen at all three levels of the ALS spinal cord, with most abundant TDP-43 deposition in the anterior gray matter of the cervical and lumbar cord. Our data show that leakage of the BSCB occurs during life, but at end-stage disease the regions with most severe BSCB damage are not those where TDP-43 accumulation is most abundant. This suggests BSCB leakage and TDP-43 pathology are independent pathologies in ALS.
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