一名患有唐氏综合征且认知保持稳定的女性的神经病理学病例报告：对神经病理学恢复力的启示

A neuropathology case report of a woman with Down syndrome who remained cognitively stable: Implications for resilience to neuropathology.

作者信息

Liou Jr-Jiun, Lou Jerry, Flores-Aguilar Lisi, Nakagiri Jamie, Yong William, Hom Christy L, Doran Eric W, Totoiu Minodora O, Lott Ira, Mapstone Mark, Keator David B, Brickman Adam M, Wright Sierra T, Nelson Brittany, Lai Florence, Xicota Laura, Dang Lam-Ha T, Li Jinghang, Santini Tales, Mettenburg Joseph M, Ikonomovic Milos D, Kofler Julia, Ibrahim Tamer, Head Elizabeth

机构信息

University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

University of California Irvine, Irvine, California, USA.

出版信息

Alzheimers Dement. 2025 Feb;21(2):e14479. doi: 10.1002/alz.14479. Epub 2025 Jan 27.

DOI:10.1002/alz.14479

PMID:39868632

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11851131/

Abstract

INTRODUCTION

Aging adults with Down syndrome (DS) accumulate Alzheimer's disease (AD) neuropathology, including amyloid beta plaques and neurofibrillary tangles, by age 40.

METHODS

We present findings from an individual with DS who remained cognitively stable despite AD neuropathology. Clinical assessments, fluid biomarkers, neuroimaging, and neuropathological examinations were conducted to characterize her condition.

RESULTS

Her apolipoprotein E was ε2/ε3 and genome-wide association study data indicated mosaicism. Neuroimaging revealed stable yet elevated amyloid and moderately elevated tau levels, while neuropathology indicated intermediate AD neuropathologic change with Lewy body and cerebrovascular pathologies. The participant demonstrated stable cognitive functioning in her 60s, potentially attributed to genetic variations, cognitive resilience, and environmental enrichment.

DISCUSSION

These findings emphasize the complexity of AD progression in DS. Further investigation into factors influencing cognitive resilience in individuals with DS is warranted. Understanding the mechanisms underlying cognitive stability in DS could offer insights into resilience to AD neuropathology in people with DS and inform future interventions.

HIGHLIGHTS

Findings from clinical assessments, fluid biomarkers, genotyping, neuroimaging, and neuropathological examinations of an individual with Down syndrome (DS) who remained cognitively stable despite Alzheimer's disease (AD) neuropathology are presented. Neuroimaging revealed stable yet elevated amyloid profiles and moderately elevated tau levels, while neuropathology indicated intermediate AD neuropathologic change with Lewy body and cerebrovascular pathologies. Despite the presence of AD pathology, the participant demonstrated intact cognitive functioning, potentially attributed to genetic variations, cognitive resilience, and environmental enrichment, emphasizing the complexity of AD progression in DS.

摘要

引言

患有唐氏综合征（DS）的老年人在40岁时就会积累阿尔茨海默病（AD）神经病理学特征，包括淀粉样β斑块和神经原纤维缠结。

方法

我们报告了一名患有DS的个体的研究结果，尽管存在AD神经病理学特征，但该个体的认知功能保持稳定。我们进行了临床评估、体液生物标志物检测、神经影像学检查和神经病理学检查，以对其病情进行特征描述。

结果

她的载脂蛋白E为ε2/ε3，全基因组关联研究数据显示存在嵌合体现象。神经影像学检查显示淀粉样蛋白水平稳定但升高，tau蛋白水平中度升高，而神经病理学检查表明存在中度AD神经病理学变化，并伴有路易体和脑血管病变。该参与者在60多岁时认知功能保持稳定，这可能归因于基因变异、认知弹性和环境丰富性。

讨论

这些发现强调了DS中AD进展的复杂性。有必要进一步研究影响DS个体认知弹性的因素。了解DS中认知稳定性的潜在机制，可能为DS患者对AD神经病理学的弹性提供见解，并为未来的干预措施提供参考。

重点

本文展示了对一名患有唐氏综合征（DS）的个体进行临床评估、体液生物标志物检测、基因分型、神经影像学检查和神经病理学检查的结果，尽管该个体存在阿尔茨海默病（AD）神经病理学特征，但其认知功能保持稳定。神经影像学检查显示淀粉样蛋白水平稳定但升高，tau蛋白水平中度升高，而神经病理学检查表明存在中度AD神经病理学变化，并伴有路易体和脑血管病变。尽管存在AD病理特征，但该参与者的认知功能完好，这可能归因于基因变异、认知弹性和环境丰富性，强调了DS中AD进展的复杂性。