{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T05:47:07Z","timestamp":1782539227167,"version":"3.54.5"},"reference-count":18,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:00:00Z","timestamp":1771027200000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's & Dementia"],"published-print":{"date-parts":[[2026,2]]},"abstract":"Abstract<\/jats:title>\n \n INTRODUCTION<\/jats:title>\n Vascular dementia (VaD) is a major therapeutic challenge. Tar DNA\u2010binding protein 43 (TDP\u201043), known for its role in neurodegeneration, may contribute to VaD pathogenesis under chronic cerebral hypoperfusion (CCH). This study investigates TDP\u201043 dysregulation in VaD.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n TDP\u201043 and phosphorylated TDP\u201043 (pTDP\u201043) expression and localization were assessed in a VaD animal model, neuronal cells exposed to oxygen\u2013glucose deprivation (OGD), and\n post mortem<\/jats:italic>\n human brain tissues.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Bilateral Common Carotid Artery Stenosis (BCAS)\u2010induced CCH led to increased pTDP\u201043 and aberrant redistribution of both TDP\u201043 and pTDP\u201043. In vitro OGD triggered similar mislocalization.\n Post mortem<\/jats:italic>\n VaD brains showed no TDP\u201043 abnormalities, while Alzheimer's and mixed dementia cases exhibited marked pathology.\n <\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n TDP\u201043 dysregulation appears early in VaD under hypoperfusive stress, distinguishing it from other dementia subtypes. These findings indicate that TDP\u201143 may warrant further investigation as a potential early molecular feature of VaD.<\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n Tar DNA\u2010binding protein 43 (TDP\u201043) is dysregulated early in vascular dementia models.<\/jats:p>\n <\/jats:list-item>\n \n Hypoperfusion triggers TDP\u201043 mislocalization and phosphorylation.<\/jats:p>\n <\/jats:list-item>\n \n TDP\u201043 pathology is absent in late\u2010stage human vascular dementia.<\/jats:p>\n <\/jats:list-item>\n \n TDP\u201043 is a transient, novel target for vascular cognitive impairment.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/alz.71196","type":"journal-article","created":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T02:25:27Z","timestamp":1771122327000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterizing TDP\u201043 involvement in vascular dementia"],"prefix":"10.1002","volume":"22","author":[{"given":"Marconi","family":"Fung","sequence":"first","affiliation":[{"name":"Department of Microbiology Anatomy Physiology and Pharmacology School of Agriculture Biomedicine and Environment La Trobe University Melbourne Australia"},{"name":"La Trobe Institute for Molecular Science La Trobe University Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuek Ling","family":"Chai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore"},{"name":"Memory Aging and Cognition Centre National University Health System Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Lin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Microbiology Anatomy Physiology and Pharmacology School of Agriculture Biomedicine and Environment La Trobe University Melbourne Australia"},{"name":"La Trobe Institute for Molecular Science La Trobe University Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishat","family":"Tabassum","sequence":"additional","affiliation":[{"name":"Department of Microbiology Anatomy Physiology and Pharmacology School of Agriculture Biomedicine and Environment La Trobe University Melbourne Australia"},{"name":"La Trobe Institute for Molecular Science La Trobe University Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vernise J. T.","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Microbiology Anatomy Physiology and Pharmacology School of Agriculture Biomedicine and Environment La Trobe University Melbourne Australia"},{"name":"La Trobe Institute for Molecular Science La Trobe University Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj N.","family":"Kalaria","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute Newcastle University Newcastle Upon Tyne United\u00a0Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong\u2010Gyu","family":"Jo","sequence":"additional","affiliation":[{"name":"School of Pharmacy Sungkyunkwan University Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher P.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore"},{"name":"Memory Aging and Cognition Centre National University Health System Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell K. P.","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore"},{"name":"Memory Aging and Cognition Centre National University Health System Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3377-0939","authenticated-orcid":false,"given":"Thiruma V.","family":"Arumugam","sequence":"additional","affiliation":[{"name":"Department of Microbiology Anatomy Physiology and Pharmacology School of Agriculture Biomedicine and Environment La Trobe University Melbourne Australia"},{"name":"La Trobe Institute for Molecular Science La Trobe University Melbourne Australia"},{"name":"School of Pharmacy Sungkyunkwan University Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-023-00640-5"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-023-01590-1"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.68304"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.12.030"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/17474930241252530"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102247"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13765"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-180644"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109581"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01963-6"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21344"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1008227107"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1134108"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-5-51"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.05190.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21425"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3109\/17482960902810890"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-025-00839-8"}],"container-title":["Alzheimer's & Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.71196","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.71196","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.71196","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T05:09:05Z","timestamp":1782536945000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.71196"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":18,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/alz.71196"],"URL":"https:\/\/doi.org\/10.1002\/alz.71196","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"2025-10-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71196"}}