{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:44:06Z","timestamp":1790117046855,"version":"4.0.1"},"reference-count":26,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,6,26]],"date-time":"2020-06-26T00:00:00Z","timestamp":1593129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01\u2010HC\u201025195"],"award-info":[{"award-number":["N01\u2010HC\u201025195"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HHSN268201500001I"],"award-info":[{"award-number":["HHSN268201500001I"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS17950"],"award-info":[{"award-number":["R01 NS17950"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG008122"],"award-info":[{"award-number":["R01 AG008122"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["K23AG038444"],"award-info":[{"award-number":["K23AG038444"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R03 AG048180\u201001A1"],"award-info":[{"award-number":["R03 AG048180\u201001A1"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG033193"],"award-info":[{"award-number":["AG033193"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1RO1 HL64753"],"award-info":[{"award-number":["1RO1 HL64753"]}],"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 HL076784"],"award-info":[{"award-number":["R01 HL076784"]}],"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":["1 R01 AG028321"],"award-info":[{"award-number":["1 R01 AG028321"]}],"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":["P30 AG010129"],"award-info":[{"award-number":["P30 AG010129"]}],"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":["NS017950"],"award-info":[{"award-number":["NS017950"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL67288"],"award-info":[{"award-number":["HL67288"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["2K24HL04334"],"award-info":[{"award-number":["2K24HL04334"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Cerebral microbleeds (CMBs) are associated with higher risk of stroke and dementia, predating clinical diagnosis by several years. CMB are considered markers of cerebral small vessel disease (CSVD): hypertensive (deep CMB) and cerebral amyloid angiopathy (lobar CMB). We related plasma <jats:italic>\u03b2<\/jats:italic>\u2010Amyloid (40, 42 and their ratio), clusterin, and tau levels to CMB to elucidate their role as biomarkers for the angiopathies represented by CMB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Dementia, stroke, and other neurological disease\u2010free Framingham Heart Study participants with available CMB and biomarker measurements were included. We related biomarker levels (standardized for analyses) to CMB presence overall and stratified by brain topography (any, lobar, deep), using multivariable logistic regression analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CMB were observed in 208 (5.7%) participants (mean age 57\u00a0years, 54% women). After multivariable adjustment, A<jats:italic>\u03b2<\/jats:italic>1\u201040 was associated with any CMB (OR (95%CI) 1.20 (0.99, 1.45) <jats:italic>P<\/jats:italic>\u00a0=\u00a00.062)) and lobar CMB (OR (95%CI) 1.33 (1.05, 1.68) <jats:italic>P<\/jats:italic>\u00a0=\u00a00.019), but not with deep CMB. Log\u2010A<jats:italic>\u03b2<\/jats:italic>1\u201042 levels were not associated with CMB overall. Clusterin was related to mixed CMB (1.70 [1.05, 2.74], <jats:italic>P<\/jats:italic>\u00a0=\u00a00.031). Tau levels were associated with any CMB (OR (95%CI) 1.26 (1.07, 1.49) <jats:italic>P<\/jats:italic>\u00a0=\u00a00.006), lobar CMB (OR (95%CI) 1.26 (1.05, 1.52) <jats:italic>P<\/jats:italic>\u00a0=\u00a00.013), and with deep CMB (OR (95% CI) 1.46 (1.13, 1.89) <jats:italic>P<\/jats:italic>\u00a0=\u00a00.004).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>We found that plasma A<jats:italic>\u03b2<\/jats:italic>1\u201040 and Tau are associated with CMB but further studies are needed to confirm their role in hemorrhage prone CSVD represented by CMB and as indicators of ongoing subclinical neuronal injury.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51066","type":"journal-article","created":{"date-parts":[[2020,6,26]],"date-time":"2020-06-26T08:33:56Z","timestamp":1593160436000},"page":"1083-1091","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Relation of plasma <i>\u03b2<\/i>\u2010amyloid, clusterin, and tau with cerebral microbleeds: Framingham Heart Study"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1101-2950","authenticated-orcid":false,"given":"Jos\u00e9 Rafael","family":"Romero","sequence":"first","affiliation":[{"name":"Department of Neurology Boston University School of Medicine Boston Massachusetts"},{"name":"NHLBI\u2019s Framingham Heart Study Framingham Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serkalem","family":"Demissie","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Boston University School of Public Health Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa","family":"Beiser","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston University School of Medicine Boston Massachusetts"},{"name":"NHLBI\u2019s Framingham Heart Study Framingham Massachusetts"},{"name":"Department of Biostatistics Boston University School of Public Health Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayandra J.","family":"Himali","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston University School of Medicine Boston Massachusetts"},{"name":"NHLBI\u2019s Framingham Heart Study Framingham Massachusetts"},{"name":"Department of Biostatistics Boston University School of Public Health Boston Massachusetts"},{"name":"Glenn Biggs Institute for Alzheimer\u2019s and Neurodegenerative Diseases University of Texas Health Sciences Center San Antonio Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"DeCarli","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California\u2010 Davis Sacramento California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Levy","sequence":"additional","affiliation":[{"name":"NHLBI\u2019s Framingham Heart Study Framingham Massachusetts"},{"name":"The Population Sciences Branch of the National Heart, Lung, and Blood Institute of the National Institutes of Health Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudha","family":"Seshadri","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston University School of Medicine Boston Massachusetts"},{"name":"NHLBI\u2019s Framingham Heart Study Framingham Massachusetts"},{"name":"Department of Biostatistics Boston University School of Public Health Boston Massachusetts"},{"name":"Glenn Biggs Institute for Alzheimer\u2019s and Neurodegenerative Diseases University of Texas Health Sciences Center San Antonio Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-002-0634-5"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.28.3.491"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70104-6"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70013-4"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/1747493017751931"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567205012666151027141730"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep26801"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003246"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2016.06.005"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1581993"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.117.019810"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-012-8237-1"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1711357114"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-017-0319-x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/1971400916689483"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-015-8381-7"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.07.001"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.008108"},{"key":"e_1_2_9_21_1","unstructured":"PaseMBA HimaliJ SatizabalC AparicioHJ DeCarliC SeshadriS. Plasma tau corresponds to preclinical Alzheimer\u2019s disease and is a strong predictor of future dementia. The American Academy of Neurology (AAN) 70th Annual Meeting April 27 2018; Los Angeles California2018."},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.114.004130"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.46.3.673"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0103351"},{"key":"e_1_2_9_25_1","first-page":"179","article-title":"Plasma amyloid beta 42\/40 ratios as biomarkers for amyloid beta cerebral deposition in cognitively normal individuals","volume":"8","author":"Fandos N","year":"2017","journal-title":"Alzheimers Dement"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20050"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40120-017-0074-8"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Facn3.51066","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51066","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acn3.51066","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51066","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T17:12:07Z","timestamp":1693847527000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.51066"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,26]]},"references-count":26,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1002\/acn3.51066"],"URL":"https:\/\/doi.org\/10.1002\/acn3.51066","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,26]]},"assertion":[{"value":"2020-01-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}