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38 Plasma proteomic signature of motoric cognitive risk syndrome

Published online by Cambridge University Press:  24 April 2023

Gabriela T. Gomez
Affiliation:
Johns Hopkins Institute for Clinical & Translational Research
Sanish Sathyan
Affiliation:
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA
Jingsha Chen
Affiliation:
Department of Epidemiology, Johns Hopkins Bloomberg, School of Public Health, Baltimore, MD, USA
Myriam Fornage
Affiliation:
Brown Foundation Institute of Molecular Medicine, McGovern Medical School and Human Genetics Center, School of Public Health The University of Texas Health Science Center at Houston, Houston, TX, USA
Pascal Schlosser
Affiliation:
Department of Epidemiology, Johns Hopkins Bloomberg, School of Public Health, Baltimore, MD, USA
Zhongsheng Peng
Affiliation:
Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD
Jenifer Cordon
Affiliation:
Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD
Priya Palta
Affiliation:
Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC
Kevin J. Sullivan
Affiliation:
Department of Medicine, Division of Geriatrics, University of Mississippi Medical Center, Jackson, MS, USA
Adrienne Tin
Affiliation:
MIND Center and Division of Nephrology, University of Mississippi Medical Center, Jackson, MS, USA
B. Gwen Windham
Affiliation:
University of Mississippi Medical Center, Jackson, MS
Rebecca F. Gottesman
Affiliation:
National Institute of Neurological Disorders and Stroke, Intramural Research Program, Bethesda, MD, USA
Josef Coresh
Affiliation:
Department of Epidemiology, Johns Hopkins Bloomberg, School of Public Health, Baltimore, MD, USA
Nir Barzilai
Affiliation:
Institute for Aging Research, Department of Medicine
Sofiya Milman
Affiliation:
Institute for Aging Research, Department of Medicine Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA
Joe Verghese
Affiliation:
Department of Neurology; Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA
Keenan A. Walker
Affiliation:
Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD
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Abstract

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OBJECTIVES/GOALS: Motoric cognitive risk (MCR) is a pre-dementia syndrome characterized by slow gait and subjective cognitive complaints. In the Atherosclerosis Risk in Communities (ARIC) study, we aim to (1) identify plasma proteins and protein modules associated with MCR and (2) compare the proteomic signature of MCR to that of mild cognitive impairment (MCI). METHODS/STUDY POPULATION: Nondemented ARIC participants were classified by MCR status (yes/no) according to a memory questionnaire and 4-meter walk. MCI status (yes/no) was classified by expert diagnosis using standardized criteria. We measured 4,877 proteins in plasma collected at ARIC Visit 5 (late-life) and Visit 2 (midlife) utilizing the SomaScan4 proteomic assay. Multivariable logistic regression”adjusted for demographic variables, kidney function, cardiovascular risk factors, and APOE4 status”related each protein to MCR at late-life. An FDR corrected P RESULTS/ANTICIPATED RESULTS: Proteome-wide association study among 4076 ARIC participants (mean age=75; 58% women, 17% Black, 4% MCR+, 21% MCI+; MCR+ and MCI+ groups overlapped) at late-life identified 26 MCR-associated proteins involved in metabolism, vascular/visceral smooth muscle, and extracellular matrix organization. At an uncorrected P DISCUSSION/SIGNIFICANCE: This proteomic characterization of MCR identifies novel plasma proteins and networks, both distinct from and overlapping with those of MCI, thus highlighting the partially divergent mechanisms underlying these pre-dementia syndromes. These findings may be leveraged toward dementia prognostication and targeted therapeutic approaches.

Type
Biostatistics, Epidemiology, and Research Design
Creative Commons
Creative Common License - CCCreative Common License - BYCreative Common License - NCCreative Common License - ND
This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is unaltered and is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use or in order to create a derivative work.
Copyright
© The Author(s), 2023. The Association for Clinical and Translational Science