{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T08:58:27Z","timestamp":1776416307361,"version":"3.51.2"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":49,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RF1 AG079569"],"award-info":[{"award-number":["RF1 AG079569"]}],"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":["R01AG071865"],"award-info":[{"award-number":["R01AG071865"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ROSMAP","award":["P30AG10161"],"award-info":[{"award-number":["P30AG10161"]}]},{"name":"ROSMAP","award":["P30AG72975"],"award-info":[{"award-number":["P30AG72975"]}]},{"name":"ROSMAP","award":["R01AG15819"],"award-info":[{"award-number":["R01AG15819"]}]},{"name":"ROSMAP","award":["R01AG17917"],"award-info":[{"award-number":["R01AG17917"]}]},{"name":"ROSMAP","award":["U01AG46152"],"award-info":[{"award-number":["U01AG46152"]}]},{"name":"ROSMAP","award":["U01AG61356"],"award-info":[{"award-number":["U01AG61356"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\u03b2-Amyloid (A\u03b2) deposition is a hallmark of both Alzheimer\u2019s disease and cerebral amyloid angiopathy. Whilst insoluble A\u03b2 aggregates have been extensively studied, the role of soluble A\u03b2 monomers in vascular amyloid pathology\u2014and their association with cognitive decline\u2014remains unclear in plaque-free brains. This study examined whether soluble cortical A\u03b2 species are associated with cognitive outcomes and amyloid-related pathologies, including cerebral amyloid angiopathy, in the absence of parenchymal A\u03b2 deposition. We examined post-mortem cortical tissue from nearly 200 individuals without parenchymal A\u03b2 deposition, drawn from two longitudinal community-based cohorts. Soluble A\u03b237, A\u03b240 and A\u03b242 were quantified by immunoassays, and total A\u03b2 levels were measured using selected reaction monitoring proteomics. Associations with semiquantitative cerebral amyloid angiopathy burden and longitudinal cognitive trajectories were assessed using regression models adjusting for age, sex and education. Higher levels of soluble A\u03b2\u2014particularly longer species such as A\u03b242, reflected by elevated A\u03b242\/40 and reduced A\u03b237\/42 ratios\u2014were significantly associated with greater cerebral amyloid angiopathy severity. Whilst immunoassay based total A\u03b2 and A\u03b2 ratio measures showed limited associations with cognitive outcomes, total A\u03b2 levels quantified by selected reaction monitoring remained significantly associated with global cognitive decline. These findings support a pathogenic role for certain soluble A\u03b2 monomers in vascular amyloid deposition. In contrast, cognitive impairment may be driven by other amyloid species such as oligomeric or extended A\u03b2 forms. A\u03b2 ratios may serve as specific markers for cerebral amyloid angiopathy and provide insights into early therapeutic strategies targeting vascular amyloid pathology.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag051","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T12:38:45Z","timestamp":1771418325000},"source":"Crossref","is-referenced-by-count":0,"title":["Association of A\u03b2 monomers with cerebral amyloid angiopathy in brains without parenchymal A\u03b2 deposition"],"prefix":"10.1093","volume":"8","author":[{"given":"Lei","family":"Liu","sequence":"first","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02139 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Yu","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center , Chicago, IL 60612 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4076-151X","authenticated-orcid":false,"given":"Vladislav A","family":"Petyuk","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, Pacific Northwest National Laboratory , Richland, WA 99354 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1911-8482","authenticated-orcid":false,"given":"Alifiya","family":"Kapasi","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center , Chicago, IL 60612 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han Bin","family":"Yoo","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02139 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana","family":"Saba","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02139 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun-Sik","family":"Yang","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02139 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7792-1698","authenticated-orcid":false,"given":"Jasmeer P","family":"Chhatwal","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02139 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3689-554X","authenticated-orcid":false,"given":"David A","family":"Bennett","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center , Chicago, IL 60612 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"issue":"7","key":"2026041703575304400_fcag051-B1","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1161\/01.STR.28.7.1418","article-title":"Diagnosis of cerebral amyloid angiopathy. 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