{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:53:05Z","timestamp":1772160785152,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T00:00:00Z","timestamp":1646784000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","award":["2016 T086"],"award-info":[{"award-number":["2016 T086"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","award":["2019 T060"],"award-info":[{"award-number":["2019 T060"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","award":["2012 T077"],"award-info":[{"award-number":["2012 T077"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01NS104147\u201002"],"award-info":[{"award-number":["5R01NS104147\u201002"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["733050822"],"award-info":[{"award-number":["733050822"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["91717337"],"award-info":[{"award-number":["91717337"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["015008048"],"award-info":[{"award-number":["015008048"]}],"id":[{"id":"10.13039\/501100001826","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":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The aim of this work is to study the association of urokinase plasminogen activator (uPA) with development and progression of cerebral amyloid angiopathy (CAA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>We studied the expression of uPA mRNA by quantitative polymerase chain reaction (qPCR) and co\u2010localisation of uPA with amyloid\u2010\u03b2 (A\u03b2) using immunohistochemistry in the cerebral vasculature of rTg\u2010DI rats compared with wild\u2010type (WT) rats and in a sporadic CAA (sCAA) patient and control subject using immunohistochemistry. Cerebrospinal fluid (CSF) uPA levels were measured in rTg\u2010DI and WT rats and in two separate cohorts of sCAA and Dutch\u2010type hereditary CAA (D\u2010CAA) patients and controls, using enzyme\u2010linked immunosorbent assays (ELISA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The presence of uPA was clearly detected in the cerebral vasculature of rTg\u2010DI rats and an sCAA patient but not in WT rats or a non\u2010CAA human control. uPA expression was highly co\u2010localised with microvascular A\u03b2 deposits. In rTg\u2010DI rats, uPA mRNA expression was highly elevated at 3\u00a0months of age (coinciding with the emergence of microvascular A\u03b2 deposition) and sustained up to 12\u2009months of age (with severe microvascular CAA deposition) compared with WT rats. CSF uPA levels were elevated in rTg\u2010DI rats compared with WT rats (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03), and in sCAA patients compared with controls (after adjustment for age of subjects,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.05 and\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03). No differences in CSF uPA levels were found between asymptomatic and symptomatic D\u2010CAA patients and their respective controls (after age\u2010adjustment,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.09 and\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.44). Increased cerebrovascular expression of uPA in CAA correlates with increased quantities of CSF uPA in rTg\u2010DI rats and human CAA patients, suggesting that uPA could serve as a biomarker for CAA.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.12804","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T22:19:07Z","timestamp":1646864347000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Elevated expression of urokinase plasminogen activator in rodent models and patients with cerebral amyloid angiopathy"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0444-662X","authenticated-orcid":false,"given":"Marc","family":"Vervuurt","sequence":"first","affiliation":[{"name":"Donders Institute for Brain, Cognition and Behaviour, Department of Neurology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyue","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, George &amp; Anne Institute for Neuroscience University of Rhode Island  Kingston Rhode Island USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Schrader","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, George &amp; Anne Institute for Neuroscience University of Rhode Island  Kingston Rhode Island USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5679-516X","authenticated-orcid":false,"given":"Anna M.","family":"de Kort","sequence":"additional","affiliation":[{"name":"Donders Institute for Brain, Cognition and Behaviour, Department of Neurology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tain\u00e1 M.","family":"Marques","sequence":"additional","affiliation":[{"name":"Donders Institute for Brain, Cognition and Behaviour, Department of Neurology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iris","family":"Kersten","sequence":"additional","affiliation":[{"name":"Donders Institute for Brain, Cognition and Behaviour, Department of Neurology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annemieke M.","family":"Peters van Ton","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilson F.","family":"Abdo","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Floris H. B. M.","family":"Schreuder","sequence":"additional","affiliation":[{"name":"Donders Institute for Brain, Cognition and Behaviour, Department of Neurology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingeborg","family":"Rasing","sequence":"additional","affiliation":[{"name":"Department of Neurology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gisela M.","family":"Terwindt","sequence":"additional","affiliation":[{"name":"Department of Neurology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marieke J. 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