{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:02:22Z","timestamp":1785240142841,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Blood\u2013brain barrier (BBB) dysfunction is an early feature of Alzheimer's disease (AD), influenced by amyloid pathology, astrocyte activation, and vasoactive mediators such as endothelin\u20101 (ET\u20101). ET\u20101 has been implicated in apoptosis and vascular senescence through induction of p53, a pro\u2010apoptotic factor, whereas BCL\u2010X exerts antiapoptotic effects. We investigated the interplay between ET\u20101, p53, and BCL\u2010X in AD and their contribution to BBB permeability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We studied 101 individuals (70 AD, 31 controls) who underwent cerebrospinal fluid (CSF) analysis for A\u03b242, p\u2010tau, ET\u20101, p53, BCL\u2010X, and the CSF\/serum albumin quotient (QAlb), an index of BBB permeability. Correlations between biomarkers were explored, followed by multiple regression and mediation analysis to assess whether p53 mediated the ET\u20101\u2013BBB relationship.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>No absolute differences in ET\u20101, p53, or BCL\u2010X were found between AD and controls. However, in AD, ET\u20101 correlated positively with p53 and negatively with BCL\u2010X, whereas no such associations were seen in controls. None of these biomarkers related to the p\u2010tau\/A\u03b242 ratio. Regression analysis identified both ET\u20101 and p53 as independent predictors of BBB permeability. Mediation analysis further revealed that ET\u20101 influenced BBB permeability both directly and indirectly through p53.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest that AD is characterized less by absolute biomarker changes and more by altered interrelationships linking ET\u20101, apoptosis, and BBB integrity. ET\u20101 may promote BBB dysfunction partly via p53, which is consistent with the mechanisms of vascular senescence. These results highlight apoptosis\u2013vascular interactions as potential drivers of BBB impairment in AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70679","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T07:10:57Z","timestamp":1784013057000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Vascular\u2013Apoptotic Crosstalk in Alzheimer's Disease: The Possible Role of Vascular Senescence in Blood\u2013Brain Barrier Dysfunction"],"prefix":"10.1111","volume":"33","author":[{"given":"Carlangelo","family":"Carrese","sequence":"first","affiliation":[{"name":"Memory Clinic and Neurodegenerative Dementia Research Unit University of Rome \u201cTor Vergata\u201d  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara Giuseppina","family":"Bonomi","sequence":"additional","affiliation":[{"name":"Memory Clinic and Neurodegenerative Dementia Research Unit University of Rome \u201cTor Vergata\u201d  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Bernocchi","sequence":"additional","affiliation":[{"name":"Memory Clinic and Neurodegenerative Dementia Research Unit University of Rome \u201cTor Vergata\u201d  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8320-2887","authenticated-orcid":false,"given":"Martina Gaia Di","family":"Donna","sequence":"additional","affiliation":[{"name":"Memory Clinic and Neurodegenerative Dementia Research Unit University of Rome \u201cTor Vergata\u201d  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4882-9895","authenticated-orcid":false,"given":"Martina","family":"Poli","sequence":"additional","affiliation":[{"name":"Memory Clinic and Neurodegenerative Dementia Research Unit University of Rome \u201cTor Vergata\u201d  Rome 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