{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T17:38:15Z","timestamp":1793295495868,"version":"4.5.0"},"reference-count":17,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec id=\"ab-zoi241562-4\"><jats:title>Importance<\/jats:title><jats:p>Baseline cerebral microbleeds (CMBs) and <jats:italic>APOE<\/jats:italic> \u03b54 allele copy number are important risk factors for amyloid-related imaging abnormalities in patients with Alzheimer disease (AD) receiving therapies to lower amyloid-\u03b2 plaque levels.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi241562-5\"><jats:title>Objective<\/jats:title><jats:p>To provide prevalence estimates of any, no more than 4, or fewer than 2 CMBs in association with amyloid status, <jats:italic>APOE<\/jats:italic> \u03b54 copy number, and age.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi241562-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This cross-sectional study used data included in the Amyloid Biomarker Study data pooling initiative (January 1, 2012, to the present [data collection is ongoing]). Data from 15 research and memory clinic studies were pooled and harmonized. Participants included individuals for whom data on age, cognitive status, amyloid status, and presence of CMBs were available. Data were analyzed from October 22, 2023, to April 26, 2024.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi241562-7\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>The main outcomes were age, cognitive status, amyloid status and presence, location, and number of CMBs. Presence of amyloid pathology was determined based on 42 amino acid\u2013long form of amyloid-\u03b2 peptide (A\u03b2<jats:sub>42<\/jats:sub>) levels in cerebrospinal fluid or on amyloid\u2013positron emission tomography. Presence and, in a subset, location (lobar vs deep) and number of CMBs were determined on magnetic resonance imaging (locally with visual rating).<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi241562-8\"><jats:title>Results<\/jats:title><jats:p>Among 4080 participants included in the analysis, the mean (SD) age was 66.5 (8.9) years, and 2241 (54.9%) were female. A total of 2973 participants had no cognitive impairment (cognitive unimpairment [CU]), and 1107 had mild cognitive impairment (MCI) or AD dementia (ADD). One thousand five hundred and thirteen participants (37.1%) had amyloid pathology, 1368 of 3599 (38.0%) with data available were <jats:italic>APOE<\/jats:italic> \u03b54 carriers, and 648 (15.9%) had CMBs. In the CU group, amyloid pathology and <jats:italic>APOE<\/jats:italic> \u03b54 copy number were not associated with presence of any, no more than 4, or fewer than 2 CMBs but were associated with increased odds of lobar CMBs (odds ratio [OR] for amyloid,\u20091.42 [95% CI, 1.20-1.69], <jats:italic>P<\/jats:italic> &amp;amp;lt; .001; OR\u2009for 2 vs 0 alleles, 1.81 [95% CI, 1.19-2.74], <jats:italic>P<\/jats:italic>\u2009=\u2009.006; OR for 1 vs 0 alleles, 1.10 [95% CI, 0.83-1.46], <jats:italic>P<\/jats:italic>\u2009=\u2009.49; and OR for 2 vs 1 allele, 1.64 [95% CI, 0.90-2.97], <jats:italic>P<\/jats:italic>\u2009=\u2009.11; overall <jats:italic>P<\/jats:italic>\u2009=\u2009.02). In the MCI-ADD group, amyloid pathology was associated with presence of any CMBs (OR,\u20091.51 [95% CI, 1.17-1.96], <jats:italic>P<\/jats:italic> = .002), no more than 4 CMBs (OR,\u20091.44 [95% CI, 1.18-1.82], <jats:italic>P<\/jats:italic> = .002), and fewer than 2 CMBs (OR 1.34 [95% CI, 1.03-1.74], <jats:italic>P<\/jats:italic> = .03) but not lobar CMBs. <jats:italic>APOE<\/jats:italic> \u03b54 copy number was associated with presence of any (OR for 2 vs 0 alleles, 1.72 [95% CI, 0.88-3.35], <jats:italic>P<\/jats:italic>\u2009=\u2009.11; OR for 1 vs 0 alleles, 0.78 [95% CI, 0.59-1.04], <jats:italic>P<\/jats:italic>\u2009=\u2009.09; and OR for 2 vs 1 allele, 2.20 [95% CI, 1.32-3.67], <jats:italic>P<\/jats:italic>\u2009=\u2009.002; overall <jats:italic>P<\/jats:italic> &amp;amp;lt; .001) and no more than 4 CMBs (OR for 2 vs 0 alleles, 1.31 [95% CI, 0.64-2.68], <jats:italic>P<\/jats:italic>\u2009=\u2009.45; OR for 1 vs 0 alleles, 0.75 [95% CI, 0.54-1.04], <jats:italic>P<\/jats:italic>\u2009=\u2009.08; and OR for 2 vs 1 allele, 1.76 [95% CI, 0.97-3.19], <jats:italic>P<\/jats:italic>\u2009=\u2009.06; overall <jats:italic>P<\/jats:italic>\u2009=\u2009.03) but not with fewer than 2 or lobar CMBs. Prevalence estimates of CMBs ranged from 6% at 50 years of age in a non\u2013<jats:italic>APOE \u03b5<\/jats:italic>4 allele carrier with no amyloid pathology and no cognitive impairment to 52% at 90 years of age in an <jats:italic>APOE \u03b5<\/jats:italic>4 homozygote carrier with amyloid pathology and cognitive impairment.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi241562-9\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>In this cross-sectional study of 4080 participants, prevalence estimates of CMBs were associated with amyloid status, <jats:italic>APOE<\/jats:italic> \u03b54 copy number, and age. CMB prevalence estimates may help inform safety evaluations for antiamyloid clinical trials.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2024.55571","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T16:33:04Z","timestamp":1737563584000},"page":"e2455571","source":"Crossref","is-referenced-by-count":7,"title":["Cerebral Microbleeds and Amyloid Pathology Estimates From the Amyloid Biomarker Study"],"prefix":"10.1001","volume":"8","author":[{"given":"Julie E.","family":"Oomens","sequence":"first","affiliation":[{"name":"Alzheimer Center Limburg, Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerle","family":"van Gils","sequence":"additional","affiliation":[{"name":"Alzheimer Center Limburg, Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie J. B.","family":"Vos","sequence":"additional","affiliation":[{"name":"Alzheimer Center Limburg, Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Whitney M.","family":"Freeze","sequence":"additional","affiliation":[{"name":"Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy N.","family":"Maserejian","sequence":"additional","affiliation":[{"name":"Research and Development, Biogen Inc, Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gioacchino","family":"Curiale","sequence":"additional","affiliation":[{"name":"Research and Development, Biogen Inc, Cambridge, 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Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Hort","sequence":"additional","affiliation":[{"name":"Department of Neurology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sterling C.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, School of Medicine and Public Health, University of Wisconsin\u2013Madison"},{"name":"Wisconsin Alzheimer\u2019s Institute, School of Medicine and Public Health, University of Wisconsin\u2013Madison"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Lle\u00f3","sequence":"additional","affiliation":[{"name":"Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain"},{"name":"Memory Unit, Neurology Department, 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