{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:48:42Z","timestamp":1775436522505,"version":"3.50.1"},"reference-count":54,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"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":["Brain Pathology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Vessel\u2010associated microglia (VAM) are an integral part of the neurovascular unit and have recently been implicated in the pathophysiology of cerebrovascular injury and blood\u2013brain barrier (BBB) leakiness in Alzheimer's disease (AD). In this neuropathological study, we explored the hypothesis that the distribution and activation of VAM are altered in AD in the presence of systemic infection, associated with cerebrovascular dysfunction. We studied VAM density in the temporal cortex and underlying white matter from AD and age\u2010matched controls with and without terminal systemic infection (SI) (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200915 per group). The area of VAM labelled with microglial markers (Iba1, HLA\u2010DR, CD68) was quantified in proximity to CD31\u2010labelled microvessels within three predefined regions: contact VAM, proximity &lt;15\u2009\u03bcm, and parenchymal &gt;15\u2009\u03bcm. The relationships between VAM and previously measured brain cytokine levels and biochemical markers of cerebral perfusion (MAG:PLP1, endothelin\u20101) and BBB leakiness (VEGF\u2010A and fibrinogen), were explored in a subset of cases. Compared to controls, the relative area of Iba1+ VAM was higher in SI and in AD. The area of HLA\u2010DR+ VAM was higher in AD only. The area of Iba1+ VAM that expressed CD68, a marker of phagocytosis, was higher in both AD and AD + SI. Iba1+ and HLA\u2010DR+ VAM\u00a0correlated inversely with anti\u2010inflammatory cytokines (IL\u201010, IL\u201023) in AD and positively with pro\u2010inflammatory cytokines (IL\u20106, IL\u201023, GM\u2010CSF, IL\u201017) in AD + SI. Iba1+ VAM density correlated positively with endothelin\u20101, VEGF\u2010A and fibrinogen in controls. HLA\u2010DR+ VAM density correlated positively with A\u03b2\n                    <jats:sub>1\u201042<\/jats:sub>\n                    in both controls and AD, and inversely with PDGFR\u03b2 and VCAM\u20101 in AD. Our data reveal the distribution of VAM is elevated in AD, and altered in the presence of systemic infection, which together are likely to be independent and synergistic contributors to cerebrovascular dysfunction in AD.\n                  <\/jats:p>","DOI":"10.1111\/bpa.70052","type":"journal-article","created":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T09:55:16Z","timestamp":1764496516000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Vessel\u2010associated microglia are differentially activated and distributed in relation to systemic infection and Alzheimer's disease"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4625-1484","authenticated-orcid":false,"given":"Oliver","family":"Milner","sequence":"first","affiliation":[{"name":"Cerebrovascular and Dementia Research Group, Translational Health Sciences, Bristol Medical School University of Bristol  Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0387-290X","authenticated-orcid":false,"given":"Robert A.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Cerebrovascular and Dementia Research Group, Translational Health Sciences, Bristol Medical School University of Bristol  Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1219-8347","authenticated-orcid":false,"given":"Daniel J.","family":"Asby","sequence":"additional","affiliation":[{"name":"Cerebrovascular and Dementia Research Group, Translational Health Sciences, Bristol Medical School University of Bristol  Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3565-0479","authenticated-orcid":false,"given":"Stephen","family":"Cross","sequence":"additional","affiliation":[{"name":"Wolfson Bioimaging Facility, Faculty of Health and Life Sciences University of Bristol  Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5884-130X","authenticated-orcid":false,"given":"Delphine","family":"Boche","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine University of Southampton  Southampton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8594-1640","authenticated-orcid":false,"given":"J. 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