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In recent years, many other diseases have been reported to have primary or secondary TDP-43 proteinopathy, such as Alzheimer\u2019s disease, Huntington\u2019s disease or the recently described limbic-predominant age-related TDP-43 encephalopathy, highlighting the need for new and accurate methods for the early detection of TDP-43 proteinopathy to help on the stratification of patients with overlapping clinical diagnosis. Currently, TDP-43 proteinopathy remains a post-mortem pathologic diagnosis. Although the main aim is to determine the pathologic TDP-43 proteinopathy in the central nervous system (CNS), the ubiquitous expression of TDP-43 in biofluids and cells outside the CNS facilitates the use of other accessible target tissues that might reflect the potential TDP-43 alterations in the brain. In this review, we describe the main developments in the early detection of TDP-43 proteinopathies, and their potential implications on diagnosis and future treatments.<\/jats:p>","DOI":"10.1186\/s40035-024-00419-8","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T08:02:01Z","timestamp":1717401721000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["In vivo diagnosis of TDP-43 proteinopathies: in search of biomarkers of clinical use"],"prefix":"10.1186","volume":"13","author":[{"given":"Juan I.","family":"L\u00f3pez-Carbonero","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Garc\u00eda-Toledo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Fern\u00e1ndez-Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Bascu\u00f1ana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda J.","family":"Gil-Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi A.","family":"Mat\u00edas-Guiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0958-0083","authenticated-orcid":false,"given":"Silvia","family":"Corrochano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,3]]},"reference":[{"issue":"7","key":"419_CR1","doi-asserted-by":"publisher","first-page":"4223","DOI":"10.1007\/s12035-022-02847-x","volume":"59","author":"YZ Liao","year":"2022","unstructured":"Liao YZ, Ma J, Dou JZ. 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