{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T01:14:01Z","timestamp":1792286041961,"version":"4.4.0"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T00:00:00Z","timestamp":1709769600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The renin\u2010angiotensin system (RAS) regulates systemic and cerebral blood flow and is dysregulated in dementia. The major aim of this study was to determine if RAS signalling is dysregulated in vascular dementia. We measured markers of RAS signalling in white matter underlying the frontal and occipital cortex in neuropathologically confirmed cases of vascular dementia (<jats:italic>n<\/jats:italic>\u2009=\u200942), Alzheimer's disease (<jats:italic>n<\/jats:italic>\u2009=\u200950), mixed AD\/VaD (<jats:italic>n<\/jats:italic>\u2009=\u200950) and age\u2010matched controls (<jats:italic>n<\/jats:italic>\u2009=\u200950). All cases were stratified according to small vessel disease (SVD) severity across both regions. ACE\u20101 and ACE\u20102 protein and activity was measured by ELISA and fluorogenic peptide assays respectively, and angiotensin peptide (Ang\u2010II, Ang\u2010III and Ang\u2010(1\u20137)) levels were measured by ELISA. ACE\u20101 protein level and enzyme activity, and Ang\u2010II and Ang\u2010III, were elevated in the white matter in vascular dementia in relation to SVD severity. ACE\u20101 and Ang\u2010II protein levels were inversely related to MAG:PLP1 ratio, a biochemical marker of brain tissue oxygenation that when reduced indicates cerebral hypoperfusion, in a subset of cases. ACE\u20102 level was elevated in frontal white matter in vascular dementia. Ang\u2010(1\u20137) level was elevated across all dementia groups compared to age\u2010matched controls but was not related to SVD severity. RAS signalling was not altered in the white matter in Alzheimer's disease. In the overlying frontal cortex, ACE\u20101 protein was reduced and ACE\u20102 protein increased in vascular dementia, whereas angiotensin peptide levels were unchanged. These data indicate that RAS signalling is dysregulated in the white matter in vascular dementia and may contribute to the pathogenesis of small vessel disease.<\/jats:p>","DOI":"10.1111\/bpa.13251","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T04:59:52Z","timestamp":1709873992000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Dysregulation of the renin\u2010angiotensin system in vascular dementia"],"prefix":"10.1111","volume":"34","author":[{"given":"H. M.","family":"Tayler","sequence":"first","affiliation":[{"name":"Dementia Research Group, Bristol Medical School University of Bristol  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O. 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