{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:02:41Z","timestamp":1789988561434,"version":"4.0.1"},"posted":{"date-parts":[[2026,9,17]]},"group-title":"Radiology and Imaging","reference-count":48,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"Intramural Research Program of the National Institutes of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>INTRODUCTION<\/jats:title>\n                  <jats:p>Determining whether plasma biomarkers are preferentially associated with Alzheimer\u2019s disease (AD)-related rather than age-related brain atrophy patterns may clarify their prognostic and diagnostic clinical use.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>\n                    Using data from the Baltimore Longitudinal Study of Aging (\n                    <jats:italic>N<\/jats:italic>\n                    =818), we examined cross-sectional plasma A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    \/A\u03b2\n                    <jats:sub>40<\/jats:sub>\n                    , GFAP, NfL, p-tau181, and p-tau217 measurements obtained while participants were cognitively unimpaired (CU). During follow-up, 104 participants developed mild cognitive impairment (MCI)\/dementia (74 due to AD, 24 due to non-AD, 6 unknown etiology). 2,293 longitudinal brain MRIs were used to quantify multidimensional atrophy pattern scores reflecting brain age (SPARE-BA), AD-like patterns (SPARE-AD), and five dominant dimensions of atrophy (R-indices). We investigated the associations of plasma biomarkers and atrophy pattern scores at index visit with conversion to MCI\/dementia due to AD. We then examined the associations of plasma biomarkers with longitudinal change in pattern scores using linear mixed effects models.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>\n                    p-tau181, A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    \/A\u03b2\n                    <jats:sub>40<\/jats:sub>\n                    (Lumipulse), and p-tau217 were associated with incident MCI\/dementia due to AD but not non-AD etiologies, while GFAP was associated with incident MCI\/dementia due to both AD and non-AD. All four biomarkers were associated with longitudinal SPARE-AD changes. A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    \/A\u03b2\n                    <jats:sub>40<\/jats:sub>\n                    (Quanterix and Lumipulse), p-tau181, and p-tau217 were associated with longitudinal parieto-temporal atrophy. p-tau217 was the only biomarker associated with longitudinal medial temporal lobe atrophy. We did not find associations between plasma biomarkers and SPARE-BA or R-indices capturing subcortical, diffuse cortical, or perisylvian atrophy.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>DISCUSSION<\/jats:title>\n                  <jats:p>Among CU individuals, plasma p-tau217 was associated with subsequent MCI\/dementia due to AD and showed the most extensive associations with longitudinal AD-related brain atrophy.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.11.26362869","type":"posted-content","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:25:24Z","timestamp":1789658724000},"source":"Crossref","is-referenced-by-count":0,"title":["Association of plasma biomarkers with longitudinal change in age- and Alzheimer\u2019s disease-related brain atrophy patterns"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5042-7422","authenticated-orcid":false,"given":"Murat","family":"Bilgel","sequence":"first","affiliation":[{"name":"Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishaan","family":"Shah","sequence":"additional","affiliation":[{"name":"Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"Cooper","sequence":"additional","affiliation":[{"name":"Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, Maryland, USA"},{"name":"Department of Psychology, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"An","sequence":"additional","affiliation":[{"name":"Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5989-9853","authenticated-orcid":false,"given":"Keenan A.","family":"Walker","sequence":"additional","affiliation":[{"name":"Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara G.","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9464-1551","authenticated-orcid":false,"given":"Abhay R.","family":"Moghekar","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 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