{"doi":"10.3389/fnins.2025.1533045","title":"TDP-43 as a potential retinal biomarker for neurodegenerative diseases","abstract":"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.","journal":"Frontiers in Neuroscience","year":2025,"id":530412,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9632,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":530674,"name":"Printha Wijesinghe","orcid":"0000-0002-6548-4689","position":1,"is_corresponding":false},{"id":747253,"name":"Joanne A. Matsubara","orcid":"0000-0002-6236-9191","position":2,"is_corresponding":false},{"id":1410126,"name":"Margit Glashutter","orcid":"0000-0002-4227-1867","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-19T02:51:05.836974Z","pmid":"40012679","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}