{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:50:46Z","timestamp":1790484646488,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Institute on Aging grants","award":["R00AG073454"],"award-info":[{"award-number":["R00AG073454"]}]},{"name":"National Institute on Aging grants","award":["R01AG082730"],"award-info":[{"award-number":["R01AG082730"]}]},{"name":"National Institute on Aging grants","award":["R00AG075317"],"award-info":[{"award-number":["R00AG075317"]}]},{"name":"National Institute on Aging grants","award":["R13AG064971"],"award-info":[{"award-number":["R13AG064971"]}]},{"name":"National Institute on Aging grants","award":["R01AG072681"],"award-info":[{"award-number":["R01AG072681"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Blood-based biomarkers for Alzheimer\u2019s disease (AD) pathology are appealing options in large population-based studies due to their low cost, minimal invasiveness, and feasibility of collection in non-clinical settings. Despite these benefits, blood-based biomarkers have lower test-retest reliability than neuroimaging measures like amyloid positron emission tomography (amyloid-PET) Centiloids; trade-offs in power and bias remain unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We use data from Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI) and the Anti-Amyloid Treatment in Asymptomatic Alzheimer\u2019s Disease (A4) studies, which include both amyloid-PET and blood-based measures, to assess differences in statistical power, required sample size, and bias when replacing a neuroimaging measure with a blood-based measure. We use simulations parameterized based on these studies to show potential implications of using plasma p-tau 181 or p-tau 217, blood-based AD biomarkers, in place of Centiloids from amyloid-PET, when the biomarker is either the exposure or the outcome in an analysis of interest.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We demonstrated that substituting amyloid-PET Centiloids with a blood-based measure of p-tau can substantially reduce power, requiring 1.5-6.5 times the sample size to achieve 80% power compared to amyloid-PET. In addition, using a blood-based biomarker as the exposure can introduce significant regression dilution bias, attenuating estimated associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>While blood-based biomarkers are lower cost and easier to collect than neuroimaging measures, their use as proxies for AD pathology may introduce substantial methodological challenges, depending on the p-tau isoform. Consideration of the sample sizes they necessitate and their potential for bias is critical for the design and interpretation of studies employing these biomarkers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/gerona\/glag068","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T12:54:05Z","timestamp":1773233645000},"source":"Crossref","is-referenced-by-count":4,"title":["Substituting blood-based biomarkers for imaging measures in Alzheimer\u2019s disease studies: implications for sample size and bias"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0181-6063","authenticated-orcid":false,"given":"Sarah F","family":"Ackley","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Brown University , Providence, Rhode Island,","place":["United 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