{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T17:17:10Z","timestamp":1789060630189,"version":"build-2803163510"},"reference-count":35,"publisher":"SAGE Publications","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,6,14]]},"abstract":"<jats:p>Background: Cerebral microbleeds (CMBs) are a common vascular pathology associated with future intracerebral hemorrhage. Plasma biomarkers of amyloid, tau, and neurodegeneration may provide a screening avenue to identify those with CMBs, but evidence is conflicting. Objective: To determine the association between plasma biomarkers (A\u03b240, A\u03b242, t-tau, p-tau181, p-tau217, neurofilament light chain (NfL)) and CMBs in a population-based study of aging and whether these biomarkers predict higher signal on A\u03b2-PET imaging in patients with multiple CMBs. Methods: 712 participants from the Mayo Clinic Study of Aging with T2* GRE MRI and plasma biomarkers were included. Biomarkers were analyzed utilizing Simoa (A\u03b240, A\u03b242, t-tau, NfL) or Meso Scale Discovery (p-tau181, p-tau217) platforms. Cross-sectional associations between CMBs, plasma biomarkers and A\u03b2-PET were evaluated using hurdle models and multivariable regression models. Results: Among the 188 (26%) individuals with\u22651 CMB, a lower plasma A\u03b242\/A\u03b240 ratio was associated with more CMBs after adjusting for covariables (IRR 568.5 95% CI 2.8\u2013116,127). No other biomarkers were associated with risk or number CMBs. In 81 individuals with\u22652 CMBs, higher plasma t-tau, p-tau181, and p-tau217 all were associated with higher A\u03b2-PET signal, with plasma p-tau217 having the strongest predictive value (r2 0.603, AIC \u201353.0). Conclusion: Lower plasma A\u03b242\/A\u03b240 ratio and higher plasma p-tau217 were associated with brain amyloidosis in individuals with CMBs from the general population. Our results suggest that in individuals with multiple CMBs and\/or lobar intracranial hemorrhage that a lower plasma A\u03b242\/A\u03b240 ratio or elevated p-tau217 may indicate underlying cerebral amyloid angiopathy.<\/jats:p>","DOI":"10.3233\/jad-220158","type":"journal-article","created":{"date-parts":[[2022,5,3]],"date-time":"2022-05-03T11:45:42Z","timestamp":1651578342000},"page":"1537-1547","source":"Crossref","is-referenced-by-count":20,"title":["Association Between Plasma Biomarkers of Amyloid, Tau, and Neurodegeneration with Cerebral Microbleeds"],"prefix":"10.1177","volume":"87","author":[{"given":"Stuart J.","family":"McCarter","sequence":"first","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN, USA"},{"name":"Center for Sleep Medicine, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy G.","family":"Lesnick","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val J.","family":"Lowe","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro A.","family":"Rabinstein","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Przybelski","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Algeciras-Schimnich","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay K.","family":"Ramanan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford R.","family":"Jack","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald C.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Knopman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley F.","family":"Boeve","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kejal","family":"Kantarci","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashanthi","family":"Vemuri","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle M.","family":"Mielke","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN, USA"},{"name":"Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Graff-Radford","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-220158_ref1","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1136\/jnnp-2016-314697","article-title":"The increasing impact of cerebral amyloid angiopathy: Essential new insights for clinical practice","volume":"88","author":"Banerjee","year":"2017","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"10.3233\/JAD-220158_ref2","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1212\/WNL.0b013e3181dad605","article-title":"Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy","volume":"74","author":"Linn","year":"2010","journal-title":"Neurology"},{"key":"10.3233\/JAD-220158_ref3","doi-asserted-by":"crossref","first-page":"e1799","DOI":"10.1212\/WNL.0000000000012770","article-title":"Cerebral amyloid angiopathy pathology and its association with amyloid-beta PET signal","volume":"97","author":"McCarter","year":"2021","journal-title":"Neurology"},{"key":"10.3233\/JAD-220158_ref4","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1007\/s00415-012-6520-8","article-title":"Interest of CSF biomarker analysis in possible cerebral amyloid angiopathy cases defined by the modified Boston criteria","volume":"259","author":"Renard","year":"2012","journal-title":"J Neurol"},{"key":"10.3233\/JAD-220158_ref5","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/ana.21694","article-title":"Cerebrospinal fluid amyloid beta(40) is decreased in cerebral amyloid angiopathy","volume":"66","author":"Verbeek","year":"2009","journal-title":"Ann Neurol"},{"key":"10.3233\/JAD-220158_ref6","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1002\/acn3.51066","article-title":"Relation of plasma \u03b2-amyloid, tau and clusterin and cerebral microbleeds: Framingham Heart Study","volume":"7","author":"Romero","year":"2020","journal-title":"Ann Clin Transl Neurol"},{"key":"10.3233\/JAD-220158_ref7","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.nbd.2003.08.019","article-title":"Hereditary cerebral hemorrhage with amyloidosis Dutch type (AbetaPP 693): Decreased plasma amyloid-beta 42 concentration","volume":"14","author":"Bornebroek","year":"2003","journal-title":"Neurobiol Dis"},{"key":"10.3233\/JAD-220158_ref8","doi-asserted-by":"crossref","first-page":"2931","DOI":"10.3390\/ijms22062931","article-title":"Plasma amyloid-beta levels in a pre-symptomatic Dutch-type hereditary cerebral amyloid angiopathy pedigree: A cross-sectional and longitudinal investigation","volume":"22","author":"Chatterjee","year":"2021","journal-title":"Int J Mol Sci"},{"key":"10.3233\/JAD-220158_ref9","doi-asserted-by":"crossref","first-page":"23727","DOI":"10.18632\/aging.103927","article-title":"Neurofilament light chain predicts risk of recurrence in cerebral amyloid angiopathy-related intracerebral hemorrhage","volume":"12","author":"Cheng","year":"2020","journal-title":"Aging (Albany NY)"},{"key":"10.3233\/JAD-220158_ref10","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1212\/01.wnl.0000191403.95453.6a","article-title":"Plasma beta-amyloid and white matter lesions in AD, MCI, and cerebral amyloid angiopathy","volume":"66","author":"Gurol","year":"2006","journal-title":"Neurology"},{"key":"10.3233\/JAD-220158_ref11","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1159\/000333811","article-title":"Plasma beta-amyloid levels in cerebral amyloid angiopathy-associated hemorrhagic stroke","volume":"10","author":"Hernandez-Guillamon","year":"2012","journal-title":"Neurodegener Dis"},{"key":"10.3233\/JAD-220158_ref12","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/j.1749-6632.2000.tb06361.x","article-title":"Plasma beta-amyloid peptide, transforming growth factor-beta 1, and risk for cerebral amyloid angiopathy","volume":"903","author":"Greenberg","year":"2000","journal-title":"Ann N Y Acad Sci"},{"key":"10.3233\/JAD-220158_ref13","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12466"},{"key":"10.3233\/JAD-220158_ref14","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1159\/000115751","article-title":"The Mayo Clinic Study of Aging: Design and sampling, participation, baseline measures and sample characteristics","volume":"30","author":"Roberts","year":"2008","journal-title":"Neuroepidemiology"},{"key":"10.3233\/JAD-220158_ref15","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1093\/aje\/kwq482","article-title":"Use of a medical records linkage system to enumerate a dynamic population over time: The Rochester Epidemiology Project","volume":"173","author":"St Sauver","year":"2011","journal-title":"Am J Epidemiol"},{"key":"10.3233\/JAD-220158_ref16","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1002\/jmri.21049","article-title":"The Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI): MRI methods","volume":"27","author":"Jack","year":"2008","journal-title":"J Magn Reson Imaging"},{"key":"10.3233\/JAD-220158_ref17","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1161\/STROKEAHA.120.031515","article-title":"Cerebral microbleeds: Relationship to antithrombotic medications","volume":"52","author":"Graff-Radford","year":"2021","journal-title":"Stroke"},{"key":"10.3233\/JAD-220158_ref18","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1161\/STROKEAHA.119.024843","article-title":"Cerebellar microbleed distribution patterns and cerebral amyloid angiopathy","volume":"50","author":"Pasi","year":"2019","journal-title":"Stroke"},{"key":"10.3233\/JAD-220158_ref19","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1002\/ana.20009","article-title":"Imaging brain amyloid in Alzheimer\u2019s disease with Pittsburgh Compound-B","volume":"55","author":"Klunk","year":"2004","journal-title":"Ann Neurol"},{"key":"10.3233\/JAD-220158_ref20","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1093\/brain\/awm336","article-title":"11C PiB and structural MRI provide complementary information in imaging of Alzheimer\u2019s disease and amnestic mild cognitive impairment","volume":"131","author":"Jack","year":"2008","journal-title":"Brain"},{"key":"10.3233\/JAD-220158_ref21","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.neuroimage.2005.02.005","article-title":"Comparison of different methodological implementations of voxel-based morphometry in neurodegenerative disease","volume":"26","author":"Senjem","year":"2005","journal-title":"Neuroimage"},{"key":"10.3233\/JAD-220158_ref22","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1001\/jamaneurol.2021.2293","article-title":"Comparison of plasma phosphorylated tau species with amyloid and tau positron emission tomography, neurodegeneration, vascular pathology, and cognitive outcomes","volume":"78","author":"Mielke","year":"2021","journal-title":"JAMA Neurol"},{"key":"10.3233\/JAD-220158_ref23","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.3233\/JAD-180582","article-title":"Epitomic characterization of the specificity of the anti-amyloid Abeta monoclonal antibodies 6E10 and 4G8","volume":"66","author":"Baghallab","year":"2018","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220158_ref24","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s13195-020-00728-w","article-title":"Comparison of ELISA- and SIMOA-based quantification of plasma Abeta ratios for early detection of cerebral amyloidosis","volume":"12","author":"De Meyer","year":"2020","journal-title":"Alzheimers Res Ther"},{"key":"10.3233\/JAD-220158_ref25","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1002\/alz.12301","article-title":"Plasma p-tau181, p-tau217, and other blood-based Alzheimer\u2019s disease biomarkers in a multi-ethnic, community study","volume":"17","author":"Brickman","year":"2021","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-220158_ref26","doi-asserted-by":"crossref","first-page":"113","DOI":"10.3233\/JAD-201536","article-title":"Cerebral amyloid angiopathy burden and cerebral microbleeds: Pathological evidence for distinct phenotypes","volume":"81","author":"Graff-Radford","year":"2021","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220158_ref27","doi-asserted-by":"crossref","first-page":"S73","DOI":"10.1007\/s40120-019-00164-5","article-title":"An update on blood-based markers of Alzheimer\u2019s disease using the SiMoA platform","volume":"8","author":"Li","year":"2019","journal-title":"Neurol Ther"},{"key":"10.3233\/JAD-220158_ref28","doi-asserted-by":"crossref","first-page":"26801","DOI":"10.1038\/srep26801","article-title":"Plasma beta-amyloid in Alzheimer\u2019s disease and vascular disease","volume":"6","author":"Janelidze","year":"2016","journal-title":"Sci Rep"},{"key":"10.3233\/JAD-220158_ref29","doi-asserted-by":"crossref","first-page":"9736","DOI":"10.1038\/s41598-021-89004-x","article-title":"Highly specific and ultrasensitive plasma test detects Abeta(1-42) and Abeta(1-40) in Alzheimer\u2019s disease","volume":"11","author":"Thijssen","year":"2021","journal-title":"Sci Rep"},{"key":"10.3233\/JAD-220158_ref30","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/S1474-4422(21)00214-3","article-title":"Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer\u2019s disease and frontotemporal lobar degeneration: A retrospective diagnostic performance study","volume":"20","author":"Thijssen","year":"2021","journal-title":"Lancet Neurol"},{"key":"10.3233\/JAD-220158_ref31","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13195-018-0404-9","article-title":"Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer\u2019s disease","volume":"10","author":"Lewczuk","year":"2018","journal-title":"Alzheimers Res Ther"},{"key":"10.3233\/JAD-220158_ref32","doi-asserted-by":"crossref","first-page":"977","DOI":"10.3233\/JAD-170458","article-title":"Plasma amyloid-beta levels, cerebral small vessel disease, and cognition: The Rotterdam Study","volume":"60","author":"Hilal","year":"2017","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220158_ref33","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1161\/STROKEAHA.117.019810","article-title":"Plasma Abeta (amyloid-beta) levels and severity and progression of small vessel disease","volume":"49","author":"van Leijsen","year":"2018","journal-title":"Stroke"},{"key":"10.3233\/JAD-220158_ref34","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1161\/STROKEAHA.113.002838","article-title":"Prognostic value of plasma beta-amyloid levels in patients with acute intracerebral hemorrhage","volume":"45","author":"Marti-Fabregas","year":"2014","journal-title":"Stroke"},{"key":"10.3233\/JAD-220158_ref35","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1161\/01.STR.0000131809.35202.1b","article-title":"Cerebral microbleeds: Prevalence and associations with cardiovascular risk factors in the Framingham Study","volume":"35","author":"Jeerakathil","year":"2004","journal-title":"Stroke"}],"container-title":["Journal of Alzheimer's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JAD-220158","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:06:05Z","timestamp":1777370765000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JAD-220158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,14]]},"references-count":35,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.3233\/jad-220158","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,14]]}}}