{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T01:15:44Z","timestamp":1792545344176,"version":"4.5.0"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T00:00:00Z","timestamp":1614211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK","doi-asserted-by":"publisher","award":["ARUK\u2010NAS2016B\u20101"],"award-info":[{"award-number":["ARUK\u2010NAS2016B\u20101"]}],"id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK","doi-asserted-by":"publisher","award":["ARUK\u2010PG2015\u201011"],"award-info":[{"award-number":["ARUK\u2010PG2015\u201011"]}],"id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In vascular dementia (VaD) and Alzheimer\u2019s disease (AD), cerebral hypoperfusion and blood\u2010brain barrier (BBB) leakiness contribute to brain damage. In this study, we have measured biochemical markers and mediators of cerebral hypoperfusion and BBB in the frontal (BA6) and parietal (BA7) cortex and underlying white matter, to investigate the pathophysiology of vascular dysfunction in AD, VaD and mixed dementia. The ratio of myelin\u2010associated glycoprotein to proteolipid protein\u20101 (MAG:PLP1), a post\u2010mortem biochemical indicator of the adequacy of ante\u2010mortem cerebral perfusion; the concentration of fibrinogen adjusted for haemoglobin level, a marker of blood\u2010brain barrier (BBB) leakiness; the level of vascular endothelial growth factor\u2010A (VEGF), a marker of tissue hypoxia; and endothelin\u20101 (EDN1), a potent vasoconstrictor, were measured by ELISA in the frontal and parietal cortex and underlying white matter in 94 AD, 20 VaD, 33 mixed dementia cases and 58 age\u2010matched controls. All cases were assessed neuropathologically for small vessel disease (SVD), cerebral amyloid angiopathy (CAA) severity, A\u03b2 and phospho\u2010tau parenchymal load, and Braak tangle stage. A\u03b240 and A\u03b242 were measured by ELISA in guanidine\u2010HCl tissue extracts. We found biochemical evidence of cerebral hypoperfusion in AD, VaD and mixed dementia to be associated with SVD, A\u03b2 level, plaque load, EDN1 level and Braak tangle stage, and to be most widespread in mixed dementia. There was evidence of BBB leakiness in AD\u2014limited to the cerebral cortex and related to EDN1 level. In conclusion, abnormalities of cerebral perfusion and BBB function in common types of dementia can largely be explained by a combination of arteriolosclerosis, and A\u03b2\u2010, tau\u2010 and endothelin\u2010related vascular dysfunction. The relative contributions of these processes vary considerably both between and within the diseases.<\/jats:p>","DOI":"10.1111\/bpa.12935","type":"journal-article","created":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T07:25:48Z","timestamp":1610263548000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Mediators of cerebral hypoperfusion and blood\u2010brain barrier leakiness in Alzheimer\u2019s disease, vascular dementia and mixed dementia"],"prefix":"10.1111","volume":"31","author":[{"given":"Hannah","family":"Tayler","sequence":"first","affiliation":[{"name":"Dementia Research Group Institute of Clinical Neurosciences Bristol Medical School University of Bristol Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8594-1640","authenticated-orcid":false,"given":"J. 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