Peripheral inflammation is associated with brain atrophy and cognitive decline linked to mild cognitive impairment and Alzheimer’s disease
Scientific Reports, vol. 14, pp. 17423
Abstract
Inflammation is an important factor in Alzheimer's disease (AD). An NMR measurement in plasma, glycoprotein acetyls (GlycA), captures the overall level of protein production and glycosylation implicated in systemic inflammation. With its additional advantage of reducing biological variability, GlycA might be useful in monitoring the relationship between peripheral inflammation and brain changes relevant to AD. However, the associations between GlycA and these brain changes have not been fully evaluated. Here, we performed Spearman's correlation analyses to evaluate these associations cross-sectionally and determined whether GlycA can inform AD-relevant longitudinal measurements among participants in the Alzheimer's Disease Neuroimaging Initiative (n = 1506), with additional linear models and stratification analyses to evaluate the influences of sex or diagnosis status and confirm findings from Spearman's correlation analyses. We found that GlycA was elevated in AD patients compared to cognitively normal participants. GlycA correlated negatively with multiple concurrent regional brain volumes in females diagnosed with late mild cognitive impairment (LMCI) or AD. Baseline GlycA level was associated with executive function decline at 3-9 year follow-up in participants diagnosed with LMCI at baseline, with similar but not identical trends observed in the future decline of memory and entorhinal cortex volume. Results here indicated that GlycA is an inflammatory biomarker relevant to AD pathogenesis and that the stage of LMCI might be relevant to inflammation-related intervention.
Authors 55
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University of California, Davis
Affiliation as printed
West Coast Metabolomics Center, Genome Center, University of California-Davis, Davis, CA, 95616, USA
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Indiana University Indianapolis · Indiana University School of Medicine · Indiana University – Purdue University Indianapolis
Affiliation as printed
Department of Radiology and Imaging Sciences and the Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
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United States Department of Agriculture · Western Human Nutrition Research Center · University of California, Davis
Affiliation as printed
Department of Nutrition, University of California-Davis, Davis, CA, 95616, USA
West Coast Metabolomics Center, Genome Center, University of California-Davis, Davis, CA, 95616, USA
Western Human Nutrition Research Center, United States Department of Agriculture-Agriculture Research Service, Davis, CA, 95616, USA
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Duke University · Helmholtz Munich · Institute of Computational Biology
Affiliation as printed
Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, 27708, USA
Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
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Baker Heart and Diabetes Institute · La Trobe University
Affiliation as printed
Baker Department of Cardiovascular Research, Translation and Implementation, La Trobe University, Bundoora, VIC, 3086, Australia
Baker Heart and Diabetes Institute, Melbourne, VIC, 3004, Australia
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Baker Heart and Diabetes Institute · La Trobe University
Affiliation as printed
Baker Department of Cardiovascular Research, Translation and Implementation, La Trobe University, Bundoora, VIC, 3086, Australia
Baker Heart and Diabetes Institute, Melbourne, VIC, 3004, Australia
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Kamil Borkowski corresponding
University of California, Davis
Affiliation as printed
West Coast Metabolomics Center, Genome Center, University of California-Davis, Davis, CA, 95616, USA. kborkowski@ucdavis.edu
West Coast Metabolomics Center, Genome Center, University of California-Davis, Davis, CA, 95616, USA
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Rima F Kaddurah-Daouk corresponding
Affiliation as printed
Department of Medicine, Duke University, Durham, NC, USA. rima.kaddurahdaouk@duke.edu
Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, 27708, USA. rima.kaddurahdaouk@duke.edu
Duke Institute of Brain Sciences, Duke University, Durham, NC, USA. rima.kaddurahdaouk@duke.edu
Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, 27708, USA
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Affiliation as printed
Duke University, Durham, USA
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Affiliation as printed
Duke University, Durham, USA
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Affiliation as printed
Duke University, Durham, USA
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Affiliation as printed
Duke University, Durham, USA
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Affiliation as printed
Duke University, Durham, USA
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Affiliation as printed
Duke University, Durham, USA
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Duke University, Durham, USA
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Indiana University School of Medicine
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Indiana University School of Medicine, Indianapolis, USA
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Indiana University School of Medicine
Affiliation as printed
Indiana University School of Medicine, Indianapolis, USA
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Helmholtz Munich · Institute of Computational Biology
Affiliation as printed
Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
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The University of Texas at San Antonio Health Science Center
Affiliation as printed
University of Texas Health Science Center San Antonio, San Antonio, USA
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Affiliation as printed
Rosa & Co., LLC, San Carlos, USA
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University of California San Diego
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University of California-San Diego, San Diego, USA
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University of California San Diego
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University of California-San Diego, San Diego, USA
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University of California, Los Angeles
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University of California-Los Angeles, Los Angeles, USA
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University of California, Los Angeles
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University of California-Los Angeles, Los Angeles, USA
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University of California, Los Angeles
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University of California-Los Angeles, Los Angeles, USA
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University of California, Los Angeles
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University of California-Los Angeles, Los Angeles, USA
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University of California, Davis
Affiliation as printed
West Coast Metabolomics Center, University of California, Davis, USA
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Icahn School of Medicine at Mount Sinai
Affiliation as printed
Icahn School of Medicine at Mount Sinai, New York, USA
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California Institute of Technology
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California Institute of Technology, Pasadena, USA
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University of Pennsylvania, Philadelphia, USA
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University of Pennsylvania, Philadelphia, USA
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Oxford University, Oxford, UK
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Oxford University, Oxford, UK
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Oxford University, Oxford, UK
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Rush University, Chicago, USA
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Rush University, Chicago, USA
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Rush University, Chicago, USA
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Rush University, Chicago, USA
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Erasmus MC, Rotterdam, The Netherlands
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Thomas Hankemeier Aachen
Affiliation as printed
Leiden University Metabolomics Center, Leiden, The Netherlands
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Ollscoil na Gaillimhe – University of Galway
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National University of Ireland, Galway, Ireland
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Institute for Systems Biology, Seattle, USA
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Purdue University West Lafayette
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Purdue University, West Lafayette, USA
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University of Hawaii Cancer Center
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University of Hawaii Cancer Center, Honolulu, USA
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The Metabolomics Innovation Centre
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The Metabolomics Innovation Centre Canada, Edmonton, Canada
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University of Arizona, Tucson, USA
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Boston University, Boston, USA
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Boston University, Boston, USA
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Boston University, Boston, USA
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Nightingale Health, Helsinki, Finland
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Biocrates Life Sciences (Austria)
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Biocrates Life Sciences AG, Innsbruck, Austria
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Cornell University · Weill Cornell Medicine
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Weill Medical College of Cornell, New York, USA
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Cornell University · Weill Cornell Medicine
Affiliation as printed
Weill Medical College of Cornell, New York, USA
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Affiliation as printed
National Centralized Repository for Alzheimer’s and Other Dementias, Indianapolis, USA
National Centralized Repository for Alzheimer's and Other Dementias, Indianapolis, USA
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Affiliation as printed
Harvard School of Public Health, Boston, USA
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