Plasma proteomic characterization of motoric cognitive risk and mild cognitive impairment

IF 11.1 1区医学 Q1 CLINICAL NEUROLOGY Alzheimer's & Dementia Pub Date : 2025-01-30 DOI:10.1002/alz.14429

Gabriela T. Gomez, Sanish Sathyan, Jingsha Chen, Myriam Fornage, Pascal Schlosser, Zhongsheng Peng, Jenifer Cordon, Priya Palta, Kevin J. Sullivan, Adrienne Tin, B. Gwen Windham, Rebecca F. Gottesman, Nir Barzilai, Sofiya Milman, Joe Verghese, Josef Coresh, Keenan A. Walker

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Abstract

INTRODUCTION

Motoric cognitive risk (MCR) is a pre-dementia syndrome characterized by mobility and cognitive dysfunction. This study conducted a proteome-wide study of MCR and compared the proteomic signatures of MCR to that of mild cognitive impairment (MCI).

METHODS

Participants were classified as MCR using a memory questionnaire and 4-meter walk. We measured 4877 plasma proteins collected during late-life and midlife. Multivariable logistic regression related each protein to late-life MCR/MCI. MCR-associated proteins were replicated internally at midlife and in an external cohort.

RESULTS

Proteome-wide analysis (n = 4076) identified 25 MCR-associated proteins. Eight of these proteins remained associated with late-life MCR when measured during midlife. Two proteins (SVEP1 and TAGLN) were externally replicated. Compared to MCI, MCR had a distinct and much stronger proteomic signature enriched for cardiometabolic and immune pathways.

DISCUSSION

Our findings highlight the divergent biology underlying two pre-dementia syndromes. Metabolic and immune dysfunction may be a primary driver of MCR.

Highlights

MCR is defined by concurrent cognitive and gait dysfunction.
MCR protein biomarkers have key roles in cardiometabolic and vascular function.
MCR biomarkers are also associated with cerebrovascular disease and dementia.
MCR and MCI demonstrate overlapping but divergent proteomic signatures.

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运动认知风险和轻度认知障碍的血浆蛋白质组学特征

运动认知风险（MCR）是一种以活动能力和认知功能障碍为特征的痴呆前期综合征。本研究对MCR进行了蛋白质组研究，并将MCR的蛋白质组学特征与轻度认知障碍（MCI）进行了比较。

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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.