{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:57:39Z","timestamp":1791928659353,"version":"4.3.4"},"reference-count":15,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01\u2010AG37491"],"award-info":[{"award-number":["R01\u2010AG37491"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    TAR DNA\u2010binding protein 43 (TDP\u201043) inclusions are defining pathological features of frontotemporal lobar degeneration (FTLD) but are also often observed in Alzheimer's disease (\n                    <jats:sc>AD<\/jats:sc>\n                    ) and primary age\u2010related tauopathy (PART). TDP\u201043 in\n                    <jats:sc>AD<\/jats:sc>\n                    is either associated with cognitive impairment or a protective\u2010life prolonging impact, and yet the localization, cellular and fragment characteristics of TDP\u201043 need to be determined. We investigated the relationships between TDP\u201043 volumetric inclusion burden in low likelihood\n                    <jats:sc>AD<\/jats:sc>\n                    (lAD) and definite PART by immunostaining against phosphorylated TDP\u201043 (pTDP\u201043), TDP\u201043 C terminal (TDP\u2010C) and TDP\u201043 N\u2010terminal (TDP\u2010N) fragments combined with 3D confocal imaging taken from eight regions: amygdala (basolateral [amygdala\u2010BL] and centromedial amygdala [amygdala\u2010CM]), the hippocampus (Cornu Ammonis [CA]\u20101, CA2\/3, CA4, dentate gyrus [DG] and subiculum [SUB]) and entorhinal cortex (ERC) and artificial intelligence (AI)\u2013based segmentation via object recognition, reconstruction and quantification. We found amygdala\u2010CM in lAD and PART to have the overall greatest burden of pTDP\u201043 whereas TDP\u2010N burden in amygdala\u2010BL of PART cases was greater than other TDP\u201043 fragments. There was no difference in TDP\u201043 burden in hippocampal subfields in PART. However, CA2\/3 region showed greater pTDP\u201043 burden while TDP\u2010N stood out in DG and SUB. Multiple comparisons among the groups revealed that TDP\u2010C was the only fragment showing differences among PART and lAD in CA2\/3, DG and SUB regions. Overall, unbiased AI\u2010based volumetric burden analysis pipeline demonstrated unique fragment aggregation patterns in the neurodegenerative processes of PART and\n                    <jats:sc>AD<\/jats:sc>\n                    .\n                  <\/jats:p>","DOI":"10.1111\/nan.70096","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T03:44:52Z","timestamp":1786419892000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Structural Heterogeneity of TDP\u201043 Fragments in Alzheimer's Disease and Primary Age\u2010Related Tauopathy by Artificial Intelligence (AI)\u2013Based 3D Segmentation"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8706-9443","authenticated-orcid":false,"given":"Gokhan","family":"Uruk","sequence":"first","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2170-6662","authenticated-orcid":false,"given":"Rodolfo G.","family":"Gatto","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9202-1172","authenticated-orcid":false,"given":"Nadia","family":"Hossain","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6914-1563","authenticated-orcid":false,"given":"Jennifer L.","family":"Whitwell","sequence":"additional","affiliation":[{"name":"Department of Radiology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Ross","family":"Reichard","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology (Neuropathology) Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2930-8634","authenticated-orcid":false,"given":"Keith A.","family":"Josephs","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"e_1_2_12_2_1","article-title":"Molecular Fragment Characteristics and Distribution of Tangle Associated TDP\u201043 (TATs) and Other TDP\u201043 Lesions in Alzheimer's Disease","volume":"4","author":"Josephs K. A.","year":"2023","journal-title":"Free Neuropathology"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp013"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-008-0477-9"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015878"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1413994112"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1951-7"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12878"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1681-2"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000304041.09418.b1"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1269-z"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30284-3"},{"key":"e_1_2_12_13_1","doi-asserted-by":"crossref","unstructured":"N.Corriveau\u2010Lecavalier H.Botha J.Graff\u2010Radford et\u00a0al. \u201cA Limbic\u2010Predominant Amnestic Neurodegenerative Syndrome Associated With TDP\u201043 Pathology \u201d medRxiv. (2023).","DOI":"10.1101\/2023.11.19.23298314"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1349-0"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-240136"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00335"}],"container-title":["Neuropathology and Applied Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.70096","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nan.70096","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.70096","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T03:41:49Z","timestamp":1789702909000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nan.70096"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":15,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1111\/nan.70096"],"URL":"https:\/\/doi.org\/10.1111\/nan.70096","archive":["Portico"],"relation":{},"ISSN":["0305-1846","1365-2990"],"issn-type":[{"value":"0305-1846","type":"print"},{"value":"1365-2990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"2026-04-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70096"}}