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However, evidence in presymptomatic AD remains elusive, underscoring the need for therapies targeting these early vascular changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We employed a multimodal approach, combining in vivo optical imaging, molecular techniques, and ex vivo magnetic resonance imaging, to investigate early capillary dysfunction in C57BL\/6\u2010Tg(Thy1\u2010APPSwDutIowa)BWevn\/Mmjax (Tg\u2010SwDI) mice without memory impairment. We also assessed the efficacy of carbonic anhydrase inhibitors (CAIs) in preventing capillary flow disturbances.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Our study revealed capillary flow disturbances associated with alterations in capillary morphology, adhesion molecule expression, and amyloid beta (A\u03b2) load in 9\u2010 to 10\u2010month\u2010old Tg\u2010SwDI mice without memory impairment. CAI treatment ameliorated these capillary flow disturbances, enhanced oxygen availability, and reduced A\u03b2 load.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These findings underscore the importance of capillary flow disturbances as early biomarkers in presymptomatic AD and highlight the potential of CAIs for preserving vascular integrity in the early stages of AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Uncovered early capillary dysfunction in a presymptomatic Alzheimer's disease (AD) mouse model.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Evidence linking capillary stalls and capillary dysfunction with oxygen delivery issues in AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Novel use of carbonic anhydrase inhibitors to prevent early capillary flow disturbances in AD.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70023","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T01:46:52Z","timestamp":1743126412000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Carbonic anhydrase inhibitors prevent presymptomatic capillary flow disturbances in a model of cerebral amyloidosis"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7509-0720","authenticated-orcid":false,"given":"Eugenio","family":"Guti\u00e9rrez\u2010Jim\u00e9nez","sequence":"first","affiliation":[{"name":"Center of Functionally Integrative Neuroscience, Department of Clinical Medicine Aarhus University  Aarhus Denmark"},{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Mondrup","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Center of Functionally Integrative Neuroscience, Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene Kl\u00e6rke","family":"Mikkelsen","sequence":"additional","affiliation":[{"name":"Center of Functionally Integrative Neuroscience, Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreekanth","family":"Kura","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Boston University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Signe K.","family":"Fruekilde","sequence":"additional","affiliation":[{"name":"Center of Functionally Integrative Neuroscience, Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Hansen","sequence":"additional","affiliation":[{"name":"Center of Functionally Integrative Neuroscience, Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Bordoni","sequence":"additional","affiliation":[{"name":"GliaLab and Letten Centre, Division of Anatomy Department of Molecular Medicine Institute of Basic Medical Sciences University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper","family":"Carlsen","sequence":"additional","affiliation":[{"name":"Research Unit for Molecular Medicine (MMF), Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Palmfeldt","sequence":"additional","affiliation":[{"name":"Research Unit for Molecular Medicine (MMF), Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Boas","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Boston University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sava","family":"Sakad\u017ei\u0107","sequence":"additional","affiliation":[{"name":"Athinoula A. 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