ArticleBrain pathology (Zurich, Switzerland)2025
Perivascular phosphorylated TDP-43 inclusions are associated with Alzheimer's disease pathology and loss of CD146 and Aquaporin-4.
Article in Brain pathology (Zurich, Switzerland), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Spatial organization of AQP4 water channel expression in the human brain.Science advances · 2026Article
- Retinal proteome changes mirror brain pathology and reveal synaptic and cytoskeletal dysfunction in Alzheimer's disease.Acta neuropathologica · 2026Article
- Region-specific features of early glial activation and Aquaporin-4 dysregulation in conditional mouse models of TDP-43 proteinopathies.Discovery immunology · 2026Article
- Amyloid beta pathology induces astrocytic pTDP-43 mislocalization and disrupts TDP-43-regulated cryptic exon transcripts.Frontiers in aging neuroscience · 2026Article
- The multifaceted roles of MCAM in development, homeostasis, pathological conditions, and cancer.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Reframing TDP-43 in Alzheimer's disease: From co-pathology to neurovascular culprit.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Structures and functions of the MICOS: Pathogenesis and therapeutic implications in Alzheimer's disease.Acta pharmaceutica Sinica. B · 2025Review
- Review
- Elevated TDP-43 serum levels associated with postoperative delirium following major cardiac surgery.Brain, behavior, & immunity - health · 2025Article
- Perivascular phosphorylated TDP-43 inclusions are associated with Alzheimer's disease pathology and loss of CD146 and Aquaporin-4.Brain pathology (Zurich, Switzerland) · 2025Article
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Abstract
The majority of patients with Alzheimer's disease (AD) exhibit aggregates of Trans-active response DNA binding protein 43 (TDP-43) in their hippocampus, which is associated with a more aggressive disease progression. The TDP-43 inclusions are commonly found in neurons, but also in astrocytes. The impact of the inclusions in astrocytes is less known. In the current study, we investigate the presence of phosphorylated TDP-43 (pTDP-43) inclusions in astrocytic endfeet and their potential association with blood-brain barrier (BBB) damage, glymphatic system dysfunction, and AD pathology. By staining postmortem hippocampal sections from AD patients and non-demented controls against TDP-43 and pTDP-43 together with the astrocytic markers glial fibrillary acidic protein (GFAP), astrocytic endfeet marker Aquaporin-4 (AQP4), and markers for BBB alterations (CD146) and leakiness (Immunoglobulin A), we demonstrate a close association between perivascular pTDP-43 or TDP-43 inclusions and GFAP or AQP4. These perivascular inclusions were more prominent in AD and correlated with the disease severity and loss of CD146 and AQP4. The findings indicate a relationship between pTDP-43 accumulation in astrocytic endfeet and BBB and glymphatic system dysfunction, which may contribute to the downstream pathological events seen in AD patients and the aggressive disease progression.
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