TDP-43 as a potential retinal biomarker for neurodegenerative diseases
TDP-43 proteinopathies are a spectrum of neurodegenerative diseases (NDDs) characterized by the pathological cytoplasmic aggregation of the TDP-43 protein. These include amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Alzheimer’s disease (AD), chronic traumatic encepha...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2025.1533045/full |
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| author | Margit Glashutter Margit Glashutter Printha Wijesinghe Joanne A. Matsubara Joanne A. Matsubara |
| author_facet | Margit Glashutter Margit Glashutter Printha Wijesinghe Joanne A. Matsubara Joanne A. Matsubara |
| author_sort | Margit Glashutter |
| collection | DOAJ |
| description | TDP-43 proteinopathies are a spectrum of neurodegenerative diseases (NDDs) characterized by the pathological cytoplasmic aggregation of the TDP-43 protein. These include amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Alzheimer’s disease (AD), chronic traumatic encephalopathy (CTE), and others. TDP-43 in the eye shows promise as a biomarker for these NDDs. Several studies have identified cytoplasmic TDP-43 inclusions in retinal layers of donors with ALS, FTLD, AD, CTE, and other conditions using immunohistochemistry. Our findings suggest that pathological aggregates of TDP-43 in the human retina are most prevalent in FTLD-TDP, ALS, and CTE, suggesting these diseases may provide the most reliable context for studying the potential of TDP-43 as a retinal biomarker. Animal model studies have been pivotal in exploring TDP-43’s roles in the retina, including its nuclear and cytoplasmic localization, RNA binding properties, and interactions with other proteins. Despite these advances, more research is needed to develop therapeutic strategies. A major limitation of human autopsy studies is the lack of corresponding brain pathology assessments to confirm TDP-43 proteinopathy diagnosis and staging. Other limitations include small sample sizes, lack of antemortem eye pathology and clinical histories, and limited comparisons across multiple NDDs. Future directions for the TDP-43 as a retinal biomarker for NDDs include retinal tracers, hyperspectral imaging, oculomics, and machine learning development. |
| format | Article |
| id | doaj-art-c8992ee46c1942a7a7ae7fb33a641872 |
| institution | Kabale University |
| issn | 1662-453X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neuroscience |
| spelling | doaj-art-c8992ee46c1942a7a7ae7fb33a6418722025-02-12T07:26:20ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-02-011910.3389/fnins.2025.15330451533045TDP-43 as a potential retinal biomarker for neurodegenerative diseasesMargit Glashutter0Margit Glashutter1Printha Wijesinghe2Joanne A. Matsubara3Joanne A. Matsubara4Department of Ophthalmology and Visual Sciences, Faculty of Medicine, Eye Care Centre, University of British Columbia, Vancouver, BC, CanadaFaculty of Medicine, University of British Columbia, Vancouver, BC, CanadaDepartment of Ophthalmology and Visual Sciences, Faculty of Medicine, Eye Care Centre, University of British Columbia, Vancouver, BC, CanadaDepartment of Ophthalmology and Visual Sciences, Faculty of Medicine, Eye Care Centre, University of British Columbia, Vancouver, BC, CanadaDjavad Mowafaghian Centre for Brain Health, The University of British Columbia, Vancouver, BC, CanadaTDP-43 proteinopathies are a spectrum of neurodegenerative diseases (NDDs) characterized by the pathological cytoplasmic aggregation of the TDP-43 protein. These include amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Alzheimer’s disease (AD), chronic traumatic encephalopathy (CTE), and others. TDP-43 in the eye shows promise as a biomarker for these NDDs. Several studies have identified cytoplasmic TDP-43 inclusions in retinal layers of donors with ALS, FTLD, AD, CTE, and other conditions using immunohistochemistry. Our findings suggest that pathological aggregates of TDP-43 in the human retina are most prevalent in FTLD-TDP, ALS, and CTE, suggesting these diseases may provide the most reliable context for studying the potential of TDP-43 as a retinal biomarker. Animal model studies have been pivotal in exploring TDP-43’s roles in the retina, including its nuclear and cytoplasmic localization, RNA binding properties, and interactions with other proteins. Despite these advances, more research is needed to develop therapeutic strategies. A major limitation of human autopsy studies is the lack of corresponding brain pathology assessments to confirm TDP-43 proteinopathy diagnosis and staging. Other limitations include small sample sizes, lack of antemortem eye pathology and clinical histories, and limited comparisons across multiple NDDs. Future directions for the TDP-43 as a retinal biomarker for NDDs include retinal tracers, hyperspectral imaging, oculomics, and machine learning development.https://www.frontiersin.org/articles/10.3389/fnins.2025.1533045/fullTDP-43 proteinopathyneurodegenerative diseasebiomarkerretinaeyebrain |
| spellingShingle | Margit Glashutter Margit Glashutter Printha Wijesinghe Joanne A. Matsubara Joanne A. Matsubara TDP-43 as a potential retinal biomarker for neurodegenerative diseases Frontiers in Neuroscience TDP-43 proteinopathy neurodegenerative disease biomarker retina eye brain |
| title | TDP-43 as a potential retinal biomarker for neurodegenerative diseases |
| title_full | TDP-43 as a potential retinal biomarker for neurodegenerative diseases |
| title_fullStr | TDP-43 as a potential retinal biomarker for neurodegenerative diseases |
| title_full_unstemmed | TDP-43 as a potential retinal biomarker for neurodegenerative diseases |
| title_short | TDP-43 as a potential retinal biomarker for neurodegenerative diseases |
| title_sort | tdp 43 as a potential retinal biomarker for neurodegenerative diseases |
| topic | TDP-43 proteinopathy neurodegenerative disease biomarker retina eye brain |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2025.1533045/full |
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