Joint spatial associations of amyloid beta and tau pathology in Down syndrome and preclinical Alzheimer's disease: Cross-sectional associations with early cognitive impairments

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-06-30 DOI:10.1002/alz.70424

Jessie Fanglu Fu, Arun Garimella, Alex Lapointe, William W. T. Aye, Charles D. Chen, Joseph H. Lee, Sharon J. Krinsky-McHale, Shahid Zaman, Ira T. Lott, Christy Hom, Beau Ances, Elizabeth Head, Mark Mapstone, Florence Lai, Benjamin L. Handen, Charles M. Laymon, Sigan L. Hartley, Bradley T. Christian, Dorene M. Rentz, Keith A. Johnson, H. Diana Rosas, Julie C. Price, the Alzheimer Biomarkers Consortium–Down Syndrome (ABC-DS)

{"title":"Joint spatial associations of amyloid beta and tau pathology in Down syndrome and preclinical Alzheimer's disease: Cross-sectional associations with early cognitive impairments","authors":"Jessie Fanglu Fu, Arun Garimella, Alex Lapointe, William W. T. Aye, Charles D. Chen, Joseph H. Lee, Sharon J. Krinsky-McHale, Shahid Zaman, Ira T. Lott, Christy Hom, Beau Ances, Elizabeth Head, Mark Mapstone, Florence Lai, Benjamin L. Handen, Charles M. Laymon, Sigan L. Hartley, Bradley T. Christian, Dorene M. Rentz, Keith A. Johnson, H. Diana Rosas, Julie C. Price, the Alzheimer Biomarkers Consortium–Down Syndrome (ABC-DS)","doi":"10.1002/alz.70424","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> INTRODUCTION</h3>\n \n <p>Individuals with Down syndrome (DS) have elevated risks for Alzheimer's disease (AD) due to amyloid beta (Aβ) precursor protein overexpression, with nearly all developing AD pathology by age 40 at autopsy. This study examined spatial associations between Aβ and tau burden in DS and neurotypical aging.</p>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p>Data included 145 DS (25–67 years) and 191 neurotypical aging individuals (63–89 years). Regional Aβ and tau positron emission tomography outcomes were analyzed using multiset canonical correlation analysis to identify joint Aβ/tau spatial patterns, with regression models assessing associations with age and cognition.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>For a given Aβ burden, cognitively stable DS individuals exhibited relatively higher tau burden than neurotypical aging, while DS mild cognitive impairment/AD individuals exhibited more widespread pathology. Joint Aβ/tau patterns were associated with episodic memory impairment in DS and, as the disease progresses, executive dysfunction.</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>DS exhibits overlapping and distinct AD-related neuropathology features, emphasizing the importance of biomarkers for early detection and intervention.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>There are distinct amyloid beta (Aβ) and tau spatial patterns in Down syndrome (DS): For a given level of Aβ burden, individuals with DS exhibited greater and more widespread tau burden compared to neurotypical aging, even before a clinical diagnosis of dementia.</li>\n \n <li>Aβ-associated tau burden was linked to episodic memory impairment in DS prior to dementia, with executive dysfunction emerging as the disease progressed, highlighting the sequential impact of pathology on cognition.</li>\n \n <li>The unique pattern of early striatal Aβ accumulation in DS supports its use as a potential biomarker for tracking disease progression and guiding clinical trial inclusion criteria for Alzheimer's disease interventions in DS.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0000,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70424","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer's & Dementia","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/alz.70424","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

Individuals with Down syndrome (DS) have elevated risks for Alzheimer's disease (AD) due to amyloid beta (Aβ) precursor protein overexpression, with nearly all developing AD pathology by age 40 at autopsy. This study examined spatial associations between Aβ and tau burden in DS and neurotypical aging.

METHODS

Data included 145 DS (25–67 years) and 191 neurotypical aging individuals (63–89 years). Regional Aβ and tau positron emission tomography outcomes were analyzed using multiset canonical correlation analysis to identify joint Aβ/tau spatial patterns, with regression models assessing associations with age and cognition.

RESULTS

For a given Aβ burden, cognitively stable DS individuals exhibited relatively higher tau burden than neurotypical aging, while DS mild cognitive impairment/AD individuals exhibited more widespread pathology. Joint Aβ/tau patterns were associated with episodic memory impairment in DS and, as the disease progresses, executive dysfunction.

DISCUSSION

DS exhibits overlapping and distinct AD-related neuropathology features, emphasizing the importance of biomarkers for early detection and intervention.

Highlights

There are distinct amyloid beta (Aβ) and tau spatial patterns in Down syndrome (DS): For a given level of Aβ burden, individuals with DS exhibited greater and more widespread tau burden compared to neurotypical aging, even before a clinical diagnosis of dementia.
Aβ-associated tau burden was linked to episodic memory impairment in DS prior to dementia, with executive dysfunction emerging as the disease progressed, highlighting the sequential impact of pathology on cognition.
The unique pattern of early striatal Aβ accumulation in DS supports its use as a potential biomarker for tracking disease progression and guiding clinical trial inclusion criteria for Alzheimer's disease interventions in DS.

Abstract Image

查看原文本刊更多论文

唐氏综合征和临床前阿尔茨海默病中β -淀粉样蛋白和tau蛋白病理的联合空间关联：与早期认知障碍的横断面关联

由于淀粉样蛋白β (Aβ)前体蛋白过度表达，唐氏综合征（DS）患者患阿尔茨海默病（AD）的风险升高，几乎所有患者在尸检时40岁时都出现AD病理。本研究探讨了退行性痴呆患者Aβ和tau负荷与神经典型衰老之间的空间关联。方法纳入145名高龄老人（25 ~ 67岁）和191名神经正常老年人（63 ~ 89岁）。使用多集典型相关分析来分析区域Aβ和tau正电子发射断层扫描结果，以确定Aβ/tau联合空间模式，并使用回归模型评估与年龄和认知的关联。结果：对于给定的a β负担，认知稳定的DS个体比神经典型衰老个体表现出相对较高的tau负担，而DS轻度认知障碍/AD个体表现出更广泛的病理。关节Aβ/tau模式与退行性痴呆的情景记忆障碍有关，并且随着疾病的进展，与执行功能障碍有关。DS表现出重叠和独特的ad相关神经病理学特征，强调了生物标志物对早期发现和干预的重要性。唐氏综合征（DS）中存在明显的β -淀粉样蛋白（a β）和tau蛋白空间模式：对于给定水平的β负担，与神经型衰老相比，唐氏综合征患者甚至在临床诊断为痴呆之前就表现出更大、更广泛的tau蛋白负担。在痴呆之前，a β相关的tau负担与DS的情景记忆障碍有关，随着疾病的进展，执行功能障碍出现，突出了病理对认知的顺序影响。DS中早期纹状体a β积累的独特模式支持其作为跟踪疾病进展的潜在生物标志物，并指导阿尔茨海默病干预的临床试验纳入标准。

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.