{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:23:00Z","timestamp":1792182180669,"version":"4.4.0"},"reference-count":61,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,5,11]],"date-time":"2022-05-11T00:00:00Z","timestamp":1652227200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019319","name":"Ressler Family Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Vascular dementia (VaD) is the accumulation of vascular lesions in the subcortical white matter of the brain. These lesions progress and there is no direct medical therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To determine the specific cellular responses in VaD so as to provide molecular targets for therapeutic development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Single\u2010nucleus transcriptome analysis was performed in human periventricular white matter (PVWM) samples of VaD and normal control (NC) subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Differential analysis shows that cell type\u2010specific transcriptomic changes in VaD are associated with the disruption of specific biological processes, including angiogenesis, immune activation, axonal injury and myelination. Each cell type in the neurovascular unit within white matter has a specific alteration in gene expression in VaD. In a central cell type for this disease, subcluster analysis of endothelial cells (EC) indicates that VaD contains a disease\u2010associated EC subcluster that expresses genes associated with programmed cell death and a response to protein folding. Two other subpopulations of EC in VaD express molecular systems associated with regenerative processes in angiogenesis, and in axonal sprouting and oligodendrocyte progenitor cell maturation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This comprehensive molecular profiling of brain samples from patients with VaD reveals previously unknown molecular changes in cells of the neurovascular niche, and an attempt at regeneration in injured white matter.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jcmm.17315","type":"journal-article","created":{"date-parts":[[2022,5,11]],"date-time":"2022-05-11T10:00:35Z","timestamp":1652263235000},"page":"3183-3195","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Single\u2010nucleus transcriptome analysis reveals disease\u2010 and regeneration\u2010associated endothelial cells in white matter vascular dementia"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5689-139X","authenticated-orcid":false,"given":"Daniel N.","family":"Mitroi","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Biobehavioral Sciences David Geffen School of Medicine at UCLA  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0460-4584","authenticated-orcid":false,"given":"Min","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Biobehavioral Sciences David Geffen School of Medicine at UCLA  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riki","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Biobehavioral Sciences David Geffen School of Medicine at UCLA  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2932-2276","authenticated-orcid":false,"given":"William E.","family":"Lowry","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell and Developmental Biology UCLA  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1169-9203","authenticated-orcid":false,"given":"S. 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