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Together, PVS enlargement, reduced amyloid-\u03b2 clearance and further accumulation form a vicious cycle underlying disease progression. Yet, the neuropathological correlates of EPVS, including the associated angioarchitecture, are poorly understood. We provide quantitative 3D reconstructions of human brain microvascular networks and their topographical associations with EPVS in large volumes of cleared human tissue spanning over the gray\/white matter interface. We reveal the existence of six vessel\/PVS morphotypes, including sinusoid and helical vessels, enclosed in increasingly enlarged PVS, and increasingly disconnected from their surrounding network. Based on the buckling of elongated structures, we discuss how they likely result from generic processes of mechanical origin, driven by white matter atrophy, thus advancing our understanding of the pathophysiological overlap between amyloid-related and cerebrovascular disease.<\/jats:p>","DOI":"10.1177\/0271678x251369256","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T12:09:31Z","timestamp":1757333371000},"page":"569-585","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["CAA-related enlarged perivascular spaces are associated with abnormal angioarchitecture in human brain tissue: A key role for white matter atrophy?"],"prefix":"10.1177","volume":"46","author":[{"given":"Marion","family":"Giraud","sequence":"first","affiliation":[{"name":"Institut de M\u00e9canique des Fluides de Toulouse (IMFT), Universit\u00e9 de Toulouse, CNRS, INPT, Universit\u00e9 Toulouse III - Paul Sabatier (UPS), Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae Hee","family":"Yun","sequence":"additional","affiliation":[{"name":"Institute for Medical Engineering and Science (IMES), Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2352-4451","authenticated-orcid":false,"given":"Leon P","family":"Munting","sequence":"additional","affiliation":[{"name":"Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital\/Harvard Medical School, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwanghun","family":"Chung","sequence":"additional","affiliation":[{"name":"Institute for Medical Engineering and Science (IMES), Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J","family":"Bacskai","sequence":"additional","affiliation":[{"name":"Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital\/Harvard Medical School, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital\/Harvard Medical School, Charlestown, MA, USA"},{"name":"Department of Neurology, J. 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