{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:55:53Z","timestamp":1790052953113,"version":"4.0.1"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>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\u2019s 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\u2019s 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.<\/jats:p>","DOI":"10.3389\/fnins.2025.1533045","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T02:29:29Z","timestamp":1739327369000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["TDP-43 as a potential retinal biomarker for neurodegenerative diseases"],"prefix":"10.3389","volume":"19","author":[{"given":"Margit","family":"Glashutter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Printha","family":"Wijesinghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne A.","family":"Matsubara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4947","DOI":"10.1093\/hmg\/ddr432","article-title":"Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation.","volume":"20","author":"Ambegaokar","year":"2011","journal-title":"Hum. 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