A systematic comparison of ATN biomarkers for monitoring longitudinal cognitive changes in Alzheimer's disease

IF 11.1 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-10-22 DOI:10.1002/alz.70783

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)

{"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. 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":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer's & Dementia","FirstCategoryId":"3","ListUrlMain":"https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.70783","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

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.

Abstract Image

查看原文本刊更多论文

监测阿尔茨海默病纵向认知变化的ATN生物标志物的系统比较

随着抗淀粉样蛋白β (Aβ)疗法被批准用于阿尔茨海默病（AD），需要替代生物标志物来监测临床治疗效果。因此，我们系统地比较了跟踪认知变化的A/T/N生物标志物（淀粉样正电子发射断层扫描[PET]、tau-PET、血浆磷酸化tau蛋白苏氨酸217 [p-tau217]和磁共振成像）的纵向变化。方法：我们分析了阿尔茨海默病神经影像学倡议（N = 141）和无症状阿尔茨海默病抗淀粉样蛋白治疗（A4）以及淀粉样蛋白风险和神经变性纵向评估（LEARN）（N = 151）的纵向生物标志物和认知变异性，使用线性混合模型进行估计。使用线性模型，我们测试了生物标志物变化作为认知变化的预测因子，并使用自举法比较了生物标志物的预测强度。结果：Tau-PET、血浆p-tau217和皮质厚度变化准确跟踪了迷你精神状态检查、阿尔茨海默病评估量表-认知亚量表13项版本、临床痴呆评分-方框总和和临床前阿尔茨海默病认知综合评分的变化率。相反，淀粉样蛋白- pet变化率与认知变化无关。讨论：血浆p-tau217提供了一种具有成本效益的AD特异性替代tau-PET，可能用于监测AD试验中的认知变化，而淀粉样蛋白pet缺乏实用性。皮质厚度的变化准确地跟踪认知变化，但可能与抗β治疗中的假性萎缩相混淆。重点：tau-PET，血浆p-tau217，皮质厚度的纵向变化-而不是淀粉样蛋白- pet -有效地追踪认知能力下降。在抗a β试验中，皮质厚度可能与假性萎缩相混淆。血浆p-tau217是tau-PET的一种稳健且经济的替代品，可作为ad特异性替代生物标志物，用于监测认知变化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

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.