{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T22:37:27Z","timestamp":1789252647434,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T00:00:00Z","timestamp":1729641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01AG066088"],"award-info":[{"award-number":["1R01AG066088"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007333","name":"Alzheimer's Disease Neuroimaging Initiative","doi-asserted-by":"publisher","award":["U01 AG024904"],"award-info":[{"award-number":["U01 AG024904"]}],"id":[{"id":"10.13039\/100007333","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Identifying low\u2010cost, minimally\u2010invasive screening instruments for Alzheimer's disease (AD) trial enrichment will improve the efficiency of AD trials.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>A total of 685 cognitively normal (CN) individuals and individuals with mild cognitive impairment (MCI) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were grouped according to cutoffs of genetic risk factor (G) polygenic hazard score (PHS) and tau pathology (T) plasma phosphorylated tau\u2010181 (p\u2010tau181) into four groups: G+T+, G\u2010T\u2010, G+T\u2010, and G\u2010T+. We assessed the associations between group level and longitudinal cognitive decline and AD conversion. Power analyses compared the estimated sample size required to detect differences in cognitive decline.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The G+T+ group was associated with faster cognitive decline and higher AD risk. Clinical trials enrolling G+T+ participants would benefit from significantly reduced sample sizes compared with similar trials using only single makers as an inclusion criterion.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>The combination of two low\u2010cost, minimally\u2010invasive measures\u2014genetics and plasma biomarkers\u2014would be a promising screening procedure for clinical trial enrollment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Participants with unimpaired or mildly impaired cognition were grouped based on cutoffs on genetic risk factors (G: polygenic hazardous score [PHS]) and Alzheimer's pathology (T: baseline plasma phosphorylated tau\u2010181 [p\u2010tau181]).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Participants with high PHSs and plasma p\u2010tau181 levels (G+T+) were at risk of faster cognitive decline and AD progression.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The combination of PHS and plasma p\u2010tau181 could enhance clinical trial enrichment more effectively than using single biomarkers.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14284","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T06:39:11Z","timestamp":1729665551000},"page":"8484-8502","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Enrichment for clinical trials of early AD: Combining genetic risk factors and plasma p\u2010tau as screening instruments"],"prefix":"10.1002","volume":"20","author":[{"given":"Xin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neuroscience University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinran","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Herbert Wertheim School of Public Health and Human Longevity Science University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven D.","family":"Edland","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of California San Diego  La Jolla California USA"},{"name":"Division of Biostatistics, Herbert Wertheim School of Public Health and Human Longevity Science University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris J.","family":"Broce","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders 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