{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T16:17:41Z","timestamp":1789402661562,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"vor","delay-in-days":85,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alz &amp; Dem Diag Ass &amp; Dis Mo"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>We examined long\u2010term plasma biomarker trajectories among participants who were cognitively unimpaired and primarily middle aged at baseline and whether trajectories differed by Alzheimer's disease (AD) genetic risk and among those who developed cognitive impairment.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Plasma amyloid beta (A\u03b2)<jats:sub>42<\/jats:sub>\/A\u03b2<jats:sub>40<\/jats:sub>, phosphorylated tau (p\u2010tau)<jats:sub>181<\/jats:sub>, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), soluble triggering receptor expressed on myeloid cells, and chitinase 3\u2010like protein 1 were measured longitudinally in 177 BIOCARD participants (<jats:italic>M<\/jats:italic> baseline age\u00a0=\u00a057.7 years; <jats:italic>M<\/jats:italic> follow\u2010up\u00a0=\u00a015.8 years), including 57 who developed cognitive impairment. Measures of AD genetic risk included apolipoprotein E (<jats:italic>APOE<\/jats:italic>) \u03b54 and an AD polygenic risk score (AD\u2010PRS).<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Compared to non\u2010carriers, <jats:italic>APOE<\/jats:italic> \u03b54 carriers had lower A\u03b2<jats:sub>42<\/jats:sub>\/A\u03b2<jats:sub>40<\/jats:sub> and greater longitudinal increases in p\u2010tau<jats:sub>181<\/jats:sub> and GFAP; in contrast, the AD\u2010PRS (excluding the <jats:italic>APOE<\/jats:italic> region) was associated with greater declines in A\u03b2<jats:sub>42<\/jats:sub>\/A\u03b2<jats:sub>40<\/jats:sub> among <jats:italic>APOE<\/jats:italic> \u03b54 non\u2010carriers. Rates of increase in p\u2010tau<jats:sub>181<\/jats:sub>, NfL, and GFAP were greater among those who later developed cognitive impairment.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Monitoring changes in plasma p\u2010tau<jats:sub>181<\/jats:sub>, NfL, and GFAP may be particularly informative during preclinical AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>We examined plasma biomarker changes in cognitively normal individuals over 15.8 years.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Apolipoprotein E (<jats:italic>APOE<\/jats:italic>) \u03b54 was related to lower amyloid beta (A\u03b2)<jats:sub>42<\/jats:sub>\/A\u03b2<jats:sub>40<\/jats:sub> and greater increases in phosphorylated tau (p\u2010tau)<jats:sub>181<\/jats:sub> and glial fibrillary acidic protein (GFAP).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In <jats:italic>APOE<\/jats:italic> \u03b54 non\u2010carriers, higher Alzheimer's disease (AD) polygenic risk score was related to greater A\u03b2<jats:sub>42<\/jats:sub>\/A\u03b2<jats:sub>40<\/jats:sub> declines.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>P\u2010tau<jats:sub>181<\/jats:sub>, NfL, and GFAP increases were greater among those who progressed to mild cognitive impairment.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Results highlight the predictive value of plasma biomarkers during preclinical AD.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/dad2.70081","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T22:21:20Z","timestamp":1743286880000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Plasma biomarker trajectories: Impact of AD genetic risk and clinical progression"],"prefix":"10.1002","volume":"17","author":[{"given":"Corinne","family":"Pettigrew","sequence":"first","affiliation":[{"name":"Department of Neurology The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Soldan","sequence":"additional","affiliation":[{"name":"Department of Neurology The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangxia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics The Johns Hopkins Bloomberg School of Public Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Hohman","sequence":"additional","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Logan","family":"Dumitrescu","sequence":"additional","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn","family":"Albert","sequence":"additional","affiliation":[{"name":"Department of Neurology The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Lab Sahlgrenska University Hospital  M\u00f6lndal Sweden"},{"name":"Paris Brain Institute ICM Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital Sorbonne University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Bittner","sequence":"additional","affiliation":[{"name":"F. 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