{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T23:21:43Z","timestamp":1792538503779,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,6,14]],"date-time":"2019-06-14T00:00:00Z","timestamp":1560470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K99 AG059893"],"award-info":[{"award-number":["K99 AG059893"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS096730"],"award-info":[{"award-number":["R01 NS096730"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 AG046657"],"award-info":[{"award-number":["R21 AG046657"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RF1 NS110054"],"award-info":[{"award-number":["RF1 NS110054"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["019.153LW.014"],"award-info":[{"award-number":["019.153LW.014"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["91619021"],"award-info":[{"award-number":["91619021"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid \u03b2 (A\u03b2) in the walls of cortical vessels and the accrual of microbleeds and microinfarcts over time. The relationship between CAA severity and microbleeds and microinfarcts as well as the sequence of events that lead to lesion formation remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We scanned intact formalin\u2010fixed hemispheres of 12 CAA cases with magnetic resonance imaging (MRI), followed by histopathological examination in predefined areas and serial sectioning in targeted areas with multiple lesions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In total, 1,168 cortical microbleeds and 472 cortical microinfarcts were observed on ex vivo MRI. Increasing CAA severity at the whole\u2010brain or regional level was not associated with the number of microbleeds or microinfarcts. However, locally, the density of A\u03b2\u2010positive cortical vessels was lower surrounding a microbleed compared to a simulated control lesion, and higher surrounding microinfarcts. Serial sectioning revealed that for (n = 28) microbleeds, both A\u03b2 (4%) and smooth muscle cells (4%) were almost never present in the vessel wall at the site of bleeding, but A\u03b2 was frequently observed upstream or downstream (71%), as was extensive fibrin(ogen) buildup (87%). In contrast, for (n = 22) microinfarcts, vascular A\u03b2 was almost always observed at the core of the lesion (91%,\n                      <jats:italic>p<\/jats:italic>\n                      &lt;\u20090.001) as well as upstream or downstream (82%), but few vessels associated with microinfarcts had intact smooth muscle cells (9%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>These observations provide a model for how a single neuropathologic process such as CAA may result in hemorrhagic or ischemic brain lesions potentially through 2 different mechanistic pathways. ANN NEUROL 2019;86:279\u2013292<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.25512","type":"journal-article","created":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T05:20:01Z","timestamp":1559366401000},"page":"279-292","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":93,"title":["Different microvascular alterations underlie microbleeds and microinfarcts"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7957-8643","authenticated-orcid":false,"given":"Susanne J.","family":"van Veluw","sequence":"first","affiliation":[{"name":"MassGeneral Institute for Neurodegenerative Disease Massachusetts General Hospital and Harvard Medical School  Charlestown MA"},{"name":"J. 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Martinos Center for Biomedical Imaging, Department of Radiology Massachusetts General Hospital  Charlestown MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Bacskai","sequence":"additional","affiliation":[{"name":"MassGeneral Institute for Neurodegenerative Disease Massachusetts General Hospital and Harvard Medical School  Charlestown MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Frosch","sequence":"additional","affiliation":[{"name":"MassGeneral Institute for Neurodegenerative Disease Massachusetts General Hospital and Harvard Medical School  Charlestown MA"},{"name":"Neuropathology Service, C. S. Kubik Laboratory for Neuropathology Massachusetts General Hospital and Harvard Medical School  Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Greenberg","sequence":"additional","affiliation":[{"name":"J. 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