{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T21:44:46Z","timestamp":1785793486941,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,31]]},"group-title":"Epidemiology","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01AG050440"],"award-info":[{"award-number":["R01AG050440"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01AG055299"],"award-info":[{"award-number":["R01AG055299"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["RF1AG051556"],"award-info":[{"award-number":["RF1AG051556"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["K24AG045334"],"award-info":[{"award-number":["K24AG045334"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P30AG059303"],"award-info":[{"award-number":["P30AG059303"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["ULT1TR001873"],"award-info":[{"award-number":["ULT1TR001873"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institue on Aging","award":["1P30AG028741"],"award-info":[{"award-number":["1P30AG028741"]}]},{"name":"National Institue on Aging","award":["P30AG066462"],"award-info":[{"award-number":["P30AG066462"]}]},{"name":"National Institue on Aging","award":["R00AG065506"],"award-info":[{"award-number":["R00AG065506"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background and Objectives<\/jats:title>\n                  <jats:p>Plasma biomarkers, particularly brain-derived phosphorylated-tau (BD-p-tau) species, hold promise as screening tools for Alzheimer\u2019s disease (AD). However, their ability to reflect AD pathology remains understudied in community settings. In a community-based sample, we examined associations between plasma biomarkers and cerebral amyloid (A\u03b2) deposition, and whether kidney function modified these associations.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    This cohort study included cognitively unimpaired, late middle-aged adults with\n                    <jats:sup>18<\/jats:sup>\n                    F-Florbetaben PET imaging and NULISAseq-derived plasma biomarker measurements. Analyses were restricted to NULISAseq biomarkers related to AD pathology (A\u03b238, A\u03b240, A\u03b242, ACHE, BACE1, BASP1, BD-p-tau181, BD-p-tau217, CD63, IGFBP7, KLK6, MAPT-tau, PSEN1, SFRP1, total p-tau181, p-tau217, and p-tau231). As a measure of kidney function, cystatin C\u2013based estimated glomerular filtration rate was calculated and categorized by chronic kidney disease (CKD) stage as normal\/high (\u226590 mL\/min\/1.73 m\n                    <jats:sup>2<\/jats:sup>\n                    ); mildly decreased (60\u201389 mL\/min\/1.73 m\n                    <jats:sup>2<\/jats:sup>\n                    ); and moderately\/severely decreased or failure (&lt;60 mL\/min\/1.73 m\n                    <jats:sup>2<\/jats:sup>\n                    ). Bidirectional stepwise linear regression analysis was performed to identify plasma biomarkers associated with brain A\u03b2 deposition. Linear regression models including plasma biomarker-by-CKD stage interactions tested effect modification by kidney function.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    A total of 541 Hispanic, non-Hispanic Black, and non-Hispanic White participants were included. Stepwise linear regression retained plasma BD-p-tau217 (B = 0.22; 95% CI 0.19 to 0.25;\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001), which was positively associated with brain A\u03b2 deposition, alongside A\u03b242 (B = \u22120.08; 95% CI \u22120.11 to \u22120.06;\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001), IGFBP7 (B = \u22120.05; 95% CI \u22120.08 to \u22120.02;\n                    <jats:italic>p<\/jats:italic>\n                    = 0.004), and BACE1 (B = \u22120.04; 95% CI \u22120.07 to \u22120.01;\n                    <jats:italic>p<\/jats:italic>\n                    = 0.009), which were negatively associated with brain A\u03b2 deposition. A significant BD-p-tau217-by-CKD stage interaction demonstrated a weaker association between BD-p-tau217 and brain A\u03b2 deposition among individuals with moderately\/severely decreased kidney function or failure than those with normal\/high kidney function (B = \u22120.17; 95% CI \u22120.25 to \u22120.08;\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>In a real-world sample, BD-p-tau217 emerged as the plasma biomarker most strongly associated with brain A\u03b2 deposition, although this association may be attenuated in the presence of moderate\/severe kidney dysfunction or kidney failure. IGFBP7 and BACE1 were identified as candidate plasma biomarkers of brain A\u03b2 deposition, warranting replication in independent cohorts.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.29.26359150","type":"posted-content","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T20:20:17Z","timestamp":1785529217000},"source":"Crossref","is-referenced-by-count":0,"title":["Association of total and brain-derived Alzheimer\u2019s disease plasma biomarkers with brain amyloid deposition in a community-based sample"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0845-933X","authenticated-orcid":false,"given":"Muge","family":"Akinci","sequence":"first","affiliation":[{"name":"Department of Medicine, College of Physicians and Surgeons, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Froogh","family":"Aziz","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Physicians and Surgeons, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Guzman","sequence":"additional","affiliation":[{"name":"Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, 710 West 168th Street, New York, NY 10032, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Cheung","sequence":"additional","affiliation":[{"name":"Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, 710 West 168th Street, New York, NY 10032, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian X.","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Physicians and Surgeons, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032, United States"},{"name":"Morris Stroud III Center for Study of Quality of Life in Health and Aging, Columbia University, 1051 Riverside Drive, New York 10032, NY, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Silver","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Physicians and Surgeons, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Eimicke","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Physicians and Surgeons, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Simoes","sequence":"additional","affiliation":[{"name":"Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, 710 West 168th Street, New York, NY 10032, United States"},{"name":"Gertrude H. 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