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To address this, we performed three-dimensional (3D) volumetric imaging of the cerebrovascular network and A\u03b2 deposition in autopsied brains with CAA using advanced tissue clearing and light-sheet fluorescence microscopy, labeling for smooth muscle actin (SMA) and A\u03b2. We found prominent A\u03b2 deposition and SMA loss in leptomeningeal and superficial cortical segments, which were anatomically contiguous with deeper A\u03b2-positive segments, indicating a surface-to-deep progression pattern of A\u03b2 extension. The perivascular plaque density was significantly lower around A\u03b2-positive vessels. This technology may provide further insights into CAA pathology and is recommended for research on the 3D pathology of neurological disorders.<\/jats:p>","DOI":"10.1126\/sciadv.aea7539","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T18:59:10Z","timestamp":1770404350000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":2,"title":["Expansive spatial pattern of A\u03b2 deposition in patients with cerebral amyloid angiopathy: A three-dimensional surface-to-depth analysis"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4693-9801","authenticated-orcid":true,"given":"Hideki","family":"Hayashi","sequence":"first","affiliation":[{"name":"Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan."},{"name":"Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7294-5183","authenticated-orcid":true,"given":"Rie","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2508-9649","authenticated-orcid":true,"given":"Akinori","family":"Miyashita","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8828-8085","authenticated-orcid":true,"given":"Takeshi","family":"Ikeuchi","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1485-0703","authenticated-orcid":true,"given":"Mari","family":"Tada","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Akazawa","sequence":"additional","affiliation":[{"name":"Department of Medical Informatics, Niigata University Medical and Dental Hospital, Niigata, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3354-5472","authenticated-orcid":true,"given":"Osamu","family":"Onodera","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Tainaka","sequence":"additional","affiliation":[{"name":"Department of System Pathology for Neurological Disorders, Brain Research Institute, Niigata University, Niigata, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4244-0277","authenticated-orcid":true,"given":"Akiyoshi","family":"Kakita","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/62.9.885"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-005-1074-9"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.08.024"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12946"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22516"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2022.30"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2215148"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43933-5"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/61.3.282"},{"key":"e_1_3_2_11_2","first-page":"75","article-title":"Amyloid-related imaging abnormalities from trials of solanezumab for Alzheimer\u2019s disease","volume":"2","author":"Carlson C.","year":"2016","unstructured":"C. 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