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In the present study, we applied a comprehensive immunohistochemical approach to investigate the structural alterations in the NVU across different Alzheimer's disease (AD) neuropathological stages. Post\u2010mortem human cortical and hippocampal samples derived from AD patients and non\u2010demented elderly control individuals were immunostained using a panel of markers representing specific components of the NVU including Collagen IV (basement membrane), PDGFR\u2010\u03b2 (pericytes), GFAP (astrocytes), Iba1 (microglia), MRC1 (perivascular macrophages) and lectin as an endothelial cell label. Astrocytes (GFAP) and microglia (Iba1) were quantified both in the whole visual\u2010field and specifically within the NVU, and the sample set was additionally analyzed using anti\u2010tau (AT8) and three different anti\u2010A\u03b2 (clones G2\u201010, G2\u201011, 4G8) antibodies. Analyses of lectin labeled sections showed an altered vascular distribution in AD patients as revealed by a reduced nearest distance between capillaries. Within the NVU, a Braak\u2010stage dependent reduction in pericyte coverage was identified as the earliest structural alteration during AD progression. In comparison to non\u2010demented elderly controls, AD patients showed a significantly higher astrocyte coverage within the NVU, which was paralleled by a reduced microglial coverage around capillaries. Assessment of perivascular macrophages moreover demonstrated a relocation of these cells from leptomeningeal arteries to penetrating parenchymal vessels in AD patients. Collectively, the results of our study represent a comprehensive first in\u2010depth analysis of AD\u2010related structural changes in the NVU and suggest distinct alterations in all components of the NVU during AD progression.<\/jats:p>","DOI":"10.1111\/bpa.12895","type":"journal-article","created":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T16:44:02Z","timestamp":1598892242000},"page":"1056-1070","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Distinct changes in all major components of the neurovascular unit across different neuropathological stages of Alzheimer's disease"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7554-3371","authenticated-orcid":false,"given":"Tunahan","family":"Kirabali","sequence":"first","affiliation":[{"name":"Institute for Regenerative Medicine University of Zurich  Schlieren Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruslan","family":"Rust","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine University of Zurich  Schlieren Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Rigotti","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine University of Zurich  Schlieren Switzerland"},{"name":"Department of Biology ETH Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Siccoli","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine University of Zurich  Schlieren Switzerland"},{"name":"Faculty of Medicine University Hospital Zurich  Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger M.","family":"Nitsch","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine University of Zurich  Schlieren Switzerland"},{"name":"Neurimmune  Schlieren Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luka","family":"Kulic","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine University of Zurich  Schlieren Switzerland"},{"name":"Roche Pharma Research &amp; Early Development F. 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