PET-measured amyloid beta accumulates at an accelerated rate in Down syndrome compared to neurotypical populations

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-06-24 DOI:10.1002/alz.70357

Andrew McVea, Alexandra DiFilippo, Max McLachlan, Brecca Betcher, Matthew Zammit, Tobey J. Betthauser, Alexander Converse, Dhanabalan Murali, Charles Stone, Sigan Hartley, Sterling Johnson, Dana L. Tudorascu, Charles M. Laymon, Ann D. Cohen, Davneet Minhas, Weiquan Luo, Chester Mathis, Patrick J. Lao, Beau Ances, Shahid Zaman, Mark Mapstone, Elizabeth Head, Benjamin L. Handen, Bradley T. Christian, ABC-DS investigators

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Abstract

INTRODUCTION

Individuals with Down syndrome (DS) have a high prevalence of Alzheimer's disease (AD) and reveal an earlier age of amyloid beta (Aβ) onset compared to sporadic AD. Differences in amyloid accumulation rates between DS and sporadic AD populations have not been established.

METHODS

Participants with ≥ 3 [C-11]PiB scans (spanning > 6 years) and transitioning to Aβ+ were included, resulting in 20 DS and 23 neurotypical (NT) participants. Amyloid accumulation was compared using global standardized uptake value ratio (SUVR) for Aβ deposition, with individual growth rates (r) estimated using the logistic growth model ( $S U V R (t) = S U V R_{B L} + \frac{K}{1 + e^{- r (t - t_{50})}}$ ).

RESULTS

The average growth rate in the DS cohort was 0.28 (0.08)/year versus 0.20 (0.08)/year for NT ( $p = . 002$ ), an increase of 40%.

DISCUSSION

Using individual longitudinal analyses, accelerated amyloid accumulation in DS is observed, This has important considerations for informing treatment trial design and monitoring beta-amyloid changes in future AD studies involving individuals with DS.

Highlights

Aβ accumulation rate was estimated using a logistic growth model.
There was no overlap in the age of amyloid positivity between DS and NT cohorts.
Participants with DS accumulate amyloid 40% faster than those with sporadic AD.

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与神经正常人群相比，pet测量的唐氏综合症患者的β淀粉样蛋白积累速度加快

唐氏综合征（DS）患者阿尔茨海默病（AD）患病率高，与散发性AD相比，β淀粉样蛋白（a β）发病年龄更早。淀粉样蛋白积累率在退行性痴呆和散发性AD人群之间的差异尚未确定。方法：3次以上[C-11]PiB扫描(跨越>；6年)，并过渡到Aβ+，结果有20名DS和23名神经正常（NT）参与者。采用Aβ沉积的全球标准化吸收值比（SUVR）比较淀粉样蛋白积累；使用logistic增长模型（S U V r (t) = S U）估计个体增长率(r)V R B L + k1 + e−r (t−t) 50) $SUVR\ （t) = SUV{{R}_{BL}} + \frac{K}{{1 + {{e}^{- R ({t - {{t}_{50}}})}}}}$）。结果：DS组的平均生长率为0.28(0.08)/年，NT组为0.20(0.08)/年（p = 0.05）。002美元p = .002美元)，增长了40%。通过个体纵向分析，观察到淀粉样蛋白在退行性痴呆中加速积累，这对于在涉及退行性痴呆个体的未来AD研究中指导治疗试验设计和监测β -淀粉样蛋白变化具有重要意义。利用logistic增长模型估计a β积累速率。DS组和NT组在淀粉样蛋白阳性年龄上没有重叠。退行性痴呆患者的淀粉样蛋白积累速度比散发性AD患者快40%。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.