{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T18:14:50Z","timestamp":1770833690764,"version":"3.50.1"},"posted":{"date-parts":[[2025,7,11]]},"group-title":"Neurology","reference-count":8,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,7,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is a common cause of late-onset dementia that does not yet have specific in vivo biomarkers. Here, we examine the biomarker potential of plasma TDP-43, measured using a highly sensitive Nucleic Acid Linked Immuno-Sandwich Assay (NULISA), in detecting advanced LATE-NC. Leveraging plasma TDP-43 and phospho-TDP-43 data from 50 deceased Religious Orders Study and the Rush Memory and Aging Project participants, we show that plasma TDP-43 and pTDP-43 were associated with advanced LATE-NC, especially in those with comorbid Alzheimer\u2019s disease neuropathologic change (ADNC): in the subgroup with autopsy-confirmed AD dementia (n=32), receiver operating characteristic area under the curve (AUC) for both plasma biomarkers approached 0.8. Plasma TDP-43 was also elevated in hippocampal sclerosis, a pathologic finding closely related to advanced LATE-NC. Together, our findings suggest the potential utility of plasma TDP-43 and pTDP-43 as biomarkers of LATE-NC, particularly in individuals with comorbid AD.<\/jats:p>","DOI":"10.1101\/2025.07.09.25331146","type":"posted-content","created":{"date-parts":[[2025,7,12]],"date-time":"2025-07-12T00:45:20Z","timestamp":1752281120000},"source":"Crossref","is-referenced-by-count":1,"title":["Plasma TDP-43 is a potential biomarker for advanced limbic-predominant age-related TDP-43 encephalopathy neuropathologic change"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9729-5404","authenticated-orcid":false,"given":"Jijing","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0258-2916","authenticated-orcid":false,"given":"Julie A.","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3689-554X","authenticated-orcid":false,"given":"David A.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4507-624X","authenticated-orcid":false,"given":"Nicholas T.","family":"Seyfried","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7846-1542","authenticated-orcid":false,"given":"Tracy L.","family":"Young-Pearse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8318-0443","authenticated-orcid":false,"given":"Hyun-Sik","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025071413352494000_2025.07.09.25331146v1.1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz099"},{"key":"2025071413352494000_2025.07.09.25331146v1.2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14202"},{"key":"2025071413352494000_2025.07.09.25331146v1.3","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-021-00503-x"},{"key":"2025071413352494000_2025.07.09.25331146v1.4","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.70001"},{"key":"2025071413352494000_2025.07.09.25331146v1.5","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12365"},{"key":"2025071413352494000_2025.07.09.25331146v1.6","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-024-00753-5"},{"key":"2025071413352494000_2025.07.09.25331146v1.7","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-179939"},{"key":"2025071413352494000_2025.07.09.25331146v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2025.03.034"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.07.09.25331146","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:40:19Z","timestamp":1768509619000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2025.07.09.25331146"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,11]]},"references-count":8,"URL":"https:\/\/doi.org\/10.1101\/2025.07.09.25331146","relation":{},"subject":[],"published":{"date-parts":[[2025,7,11]]},"subtype":"preprint"}}