Davina Biel, Anna Steward, Anna Dewenter, Amir Dehsarvi, Zeyu Zhu, Sebastian N Roemer-Cassiano, Lukas Frontzkowski, Fabian Hirsch, Carla Palleis, Günter Höglinger, Matthias Brendel, Nicolai Franzmeier, for the Alzheimer's Disease Neuroimaging Initiative (ADNI)
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Therefore, we systematically compared longitudinal changes in A/T/N biomarkers (amyloid-positron emission tomography [PET], tau-PET, plasma phosphorylated tau at threonine 217 [p-tau<sub>217</sub>], and magnetic resonance imaging) for tracking cognitive changes.</p>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p>We analyzed longitudinal biomarker and cognitive change rates from the Alzheimer's Disease Neuroimaging Initiative (<i>N </i>= 141) and Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) (<i>N</i> = 151), estimated using linear mixed models. Using linear models, we tested biomarker changes as predictors of cognitive changes, comparing predictive strengths across biomarkers using bootstrapping.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>Tau-PET, plasma p-tau217, and cortical thickness changes accurately tracked change rates in Mini-Mental State Examination, Alzheimer's Disease Assessment Scale-Cognitive Subscale 13-item version, Clinical Dementia Rating-Sum of Boxes, and Preclinial Alzheimer Cognitive Composite scores. In contrast, amyloid-PET change rates were not linked to cognitive changes.</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>Plasma p-tau<sub>217</sub> offers a cost-effective AD-specific alternative to tau-PET and could potentially be implemented for monitoring cognitive changes in AD trials, while amyloid-PET lacks utility. Cortical thickness changes accurately track cognitive changes but may be confounded by pseudo-atrophy in anti-Aβ treatments.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>Longitudinal changes in tau-PET, plasma p-tau<sub>217</sub>, cortical thickness – but not amyloid-PET – effectively track cognitive decline.</li>\n \n <li>Cortical thickness may be confounded by pseudo-atrophy in anti-Aβ trials.</li>\n \n <li>Plasma p-tau<sub>217</sub> is a robust and cost-effective alternative to tau-PET as an AD-specific surrogate biomarker for monitoring cognitive changes.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1000,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70783","citationCount":"0","resultStr":"{\"title\":\"A systematic comparison of ATN biomarkers for monitoring longitudinal cognitive changes in Alzheimer's disease\",\"authors\":\"Davina Biel, Anna Steward, Anna Dewenter, Amir Dehsarvi, Zeyu Zhu, Sebastian N Roemer-Cassiano, Lukas Frontzkowski, Fabian Hirsch, Carla Palleis, Günter Höglinger, Matthias Brendel, Nicolai Franzmeier, for the Alzheimer's Disease Neuroimaging Initiative (ADNI)\",\"doi\":\"10.1002/alz.70783\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> INTRODUCTION</h3>\\n \\n <p>With anti-amyloid beta (Aβ) therapies approved for Alzheimer's disease (AD), surrogate biomarkers are needed to monitor clinical treatment efficacy. 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A systematic comparison of ATN biomarkers for monitoring longitudinal cognitive changes in Alzheimer's disease
INTRODUCTION
With anti-amyloid beta (Aβ) therapies approved for Alzheimer's disease (AD), surrogate biomarkers are needed to monitor clinical treatment efficacy. Therefore, we systematically compared longitudinal changes in A/T/N biomarkers (amyloid-positron emission tomography [PET], tau-PET, plasma phosphorylated tau at threonine 217 [p-tau217], and magnetic resonance imaging) for tracking cognitive changes.
METHODS
We analyzed longitudinal biomarker and cognitive change rates from the Alzheimer's Disease Neuroimaging Initiative (N = 141) and Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) (N = 151), estimated using linear mixed models. Using linear models, we tested biomarker changes as predictors of cognitive changes, comparing predictive strengths across biomarkers using bootstrapping.
RESULTS
Tau-PET, plasma p-tau217, and cortical thickness changes accurately tracked change rates in Mini-Mental State Examination, Alzheimer's Disease Assessment Scale-Cognitive Subscale 13-item version, Clinical Dementia Rating-Sum of Boxes, and Preclinial Alzheimer Cognitive Composite scores. In contrast, amyloid-PET change rates were not linked to cognitive changes.
DISCUSSION
Plasma p-tau217 offers a cost-effective AD-specific alternative to tau-PET and could potentially be implemented for monitoring cognitive changes in AD trials, while amyloid-PET lacks utility. Cortical thickness changes accurately track cognitive changes but may be confounded by pseudo-atrophy in anti-Aβ treatments.
Highlights
Longitudinal changes in tau-PET, plasma p-tau217, cortical thickness – but not amyloid-PET – effectively track cognitive decline.
Cortical thickness may be confounded by pseudo-atrophy in anti-Aβ trials.
Plasma p-tau217 is a robust and cost-effective alternative to tau-PET as an AD-specific surrogate biomarker for monitoring cognitive changes.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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