ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1576373
Blood biomarker as surrogate endpoint in Alzheimer's disease research
Provisionally accepted
- 1University of Florida, Gainesville, United States
- 2Chongqing Medical Electronic Engineering Technology Research Center, Chongqing University, Chongqing, Chongqing, China
- 3Washington University in St. Louis, St. Louis, Missouri, United States
- 4Cleveland Clinic, Cleveland, Ohio, United States
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Background: Blood biomarkers for Alzheimer's disease (AD) can be utilized as surrogate endpoints to speed therapeutic development for AD.We assessed the association between short-term change of blood biomarkers and long-term decline in cognitive and brain structure volume measures by using the ADNI database, with the focus on amyloid-β (Aβ) positive participants. In the statistical models, association was calculated after controlling for age, sex, and other possible confounding covariates. We removed outliers before running statistical models to have robust results.Results: A trend association was found between the change of plasma neurofilament light (NfL) at 12 months and the change of Mini-Mental State Examination (MMSE) at 24 months for Aβ positive MCI patients. For Aβ positive dementia patients, a trend association was observed between the change of plasma p-tau181 and the changes in whole brain and middle temporal.Conclusions: Increased plasma levels of NfL or p-tau181 blood biomarker were found to be associated with a limited number of reduced brain volumes and/or declined cognitive outcomes, suggesting that blood biomarkers may have a predictive role in AD trials.
Keywords: Alzheimer's disease, blood biomarkers, Cognitive measures, NFL, P-tau181, Surrogate endpoint
Received: 13 Feb 2025; Accepted: 23 Apr 2025.
Copyright: © 2025 Shan, Li, Zhang, Wang and Bernick. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Guogen Shan, University of Florida, Gainesville, United States
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