{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T06:34:37Z","timestamp":1783233277805,"version":"3.54.6"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Blood biomarkers for Alzheimer\u2019s disease (AD) can be utilized as surrogate endpoints to accelerate therapeutic development for this condition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We assessed the association between short-term changes in blood biomarkers and long-term declines in cognitive and brain structure volume measures using the ADNI database, with a focus on amyloid-<jats:italic>\u03b2<\/jats:italic> (A<jats:italic>\u03b2<\/jats:italic>)-positive participants. In our statistical models, the association was calculated after controlling for age, sex, and other possible confounding covariates. Additionally, outliers were removed before running the statistical models to ensure that the results were robust.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A trend association was found between changes in the levels of plasma neurofilament light (NfL) at 12\u202fmonths and changes in the scores on the Mini-Mental State Examination (MMSE) at 24\u202fmonths in A\u03b2-positive mild cognitive impairment (MCI) patients. For A<jats:italic>\u03b2-<\/jats:italic>positive dementia patients, a trend association was observed between changes in plasma p-tau181 levels and changes in whole brain and middle temporal volume.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Increased plasma levels of NfL or p-tau181 blood biomarkers were found to be associated with reduced brain volumes and\/or declined cognitive outcomes, suggesting that these blood biomarkers may have a predictive role in AD trials.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2025.1576373","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T05:35:03Z","timestamp":1746768903000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Blood biomarkers as surrogate endpoints in Alzheimer\u2019s disease research"],"prefix":"10.3389","volume":"17","author":[{"given":"Guogen","family":"Shan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Bernick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1001\/jamaneurol.2023.5319","article-title":"Diagnostic accuracy of a plasma phosphorylated tau 217 immunoassay for Alzheimer disease pathology","volume":"81","author":"Ashton","year":"2024","journal-title":"JAMA Neurol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1007\/s00401-021-02275-6","article-title":"Plasma p-tau 231: a new biomarker for incipient Alzheimer\u2019s disease pathology","volume":"141","author":"Ashton","year":"2021","journal-title":"Acta Neuropathol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. 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