Plasma proteomic signatures of dual cognitive and mobility decline in older adults.

IF 10.8 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

EBioMedicine Pub Date : 2025-08-01 Epub Date: 2025-08-04 DOI:10.1016/j.ebiom.2025.105858

Qu Tian, Erin E Greig, Michael R Duggan, Keenan A Walker, Luigi Ferrucci

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引用次数: 0

Abstract

Background: The simultaneous memory and gait decline is linked to greater dementia risk than memory decline alone. We aim to identify dual decline-related protein changes that may offer valuable insights into biological processes.

Methods: We compared longitudinal changes in 7268 plasma proteomic markers in older adults experiencing dual decline, memory decline, and gait decline from no decline (reference) using linear mixed-effects regression and related to brain MRI and blood biomarkers.

Findings: There were no baseline group differences in proteins. Longitudinally, only dual decline showed significant changes in 75 proteins, with PGP9.5 showing the most alteration (p-FDR < 0.05), implicated in synaptic function, proteostasis, and regulation of amyloid precursor protein and amyloid β protein. The top-enriched pathway pointed to mitochondrial protein degradation. Of 75, changes in select proteins were related to future cognitive impairment, brain atrophy patterns, and blood biomarkers of AD, neuroinflammation, and neurodegeneration, with TRI72 being the top significant protein related to cognitive impairment and pTau181 progression.

Interpretation: Older adults experiencing dual decline exhibit longitudinal protein changes, indicating mitochondrial dysfunction, proteostasis, neuroinflammation, and immune responses.

Funding: None.

查看原文本刊更多论文

老年人双重认知和活动能力下降的血浆蛋白质组学特征。

背景：记忆力和步态同时下降比单独记忆力下降更容易导致痴呆。我们的目标是确定双重下降相关的蛋白质变化，这可能为生物过程提供有价值的见解。方法：我们使用线性混合效应回归，并与脑MRI和血液生物标志物相关，比较了7268个血浆蛋白质组学标志物的纵向变化，这些老年人经历了双重衰退、记忆衰退和步态衰退（参考）。结果：在蛋白质方面没有基线组差异。纵向上，75种蛋白只有双重下降表现出显著的变化，其中PGP9.5变化最大（p-FDR < 0.05），涉及突触功能、蛋白质平衡以及淀粉样蛋白前体蛋白和淀粉样蛋白β的调节。顶部富集的途径指向线粒体蛋白降解。在75种蛋白质中，选定蛋白质的变化与未来的认知障碍、脑萎缩模式以及AD、神经炎症和神经退行性变的血液生物标志物相关，其中TRI72是与认知障碍和pTau181进展相关的最重要蛋白质。解释：经历双重衰退的老年人表现出纵向蛋白质变化，表明线粒体功能障碍、蛋白质停滞、神经炎症和免疫反应。资金:没有。

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

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.