{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:22:16Z","timestamp":1791872536426,"version":"4.3.4"},"reference-count":62,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"16","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,4,18]]},"abstract":"<jats:p>\n            Mutations in the\n            <jats:italic>TARDBP<\/jats:italic>\n            gene encoding TDP-43 protein are linked to loss of function in neurons and familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). We recently identified reduced nuclear TDP-43 in capillary endothelial cells (ECs) of donors with ALS-FTD. Because blood-brain barrier (BBB) permeability increases in ALS-FTD, we postulated that reduced nuclear TDP-43 in ECs might contribute. Here, we show that nuclear TDP-43 is reduced in ECs of mice with an ALS-FTD\u2013associated mutation in TDP-43 (\n            <jats:italic>\n              Tardbp\n              <jats:sup>G348C<\/jats:sup>\n            <\/jats:italic>\n            ) and that this leads to cell-autonomous loss of junctional complexes and BBB integrity. Targeted excision of TDP-43 in brain ECs recapitulates BBB defects and loss of junctional complexes and ultimately leads to fibrin deposition, gliosis, phospho-Tau accumulation, and impaired memory and social interaction. Transcriptional changes in TDP-43\u2013deficient ECs resemble diseased brain ECs. These data show that nuclear loss of TDP-43 in brain ECs disrupts the BBB and causes hallmarks of FTD.\n          <\/jats:p>","DOI":"10.1126\/sciadv.ads0505","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T17:58:56Z","timestamp":1744826336000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":22,"title":["Amyotrophic lateral sclerosis and frontotemporal dementia mutation reduces endothelial TDP-43 and causes blood-brain barrier defects"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2259-2839","authenticated-orcid":true,"given":"Ashok","family":"Cheemala","sequence":"first","affiliation":[{"name":"Center for Vascular Biology, University of Connecticut School of Medicine, Farmington, CT, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0100-4906","authenticated-orcid":true,"given":"Amy 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