Differences in plasma metabolites related to Alzheimer's disease, APOE ε4 status, and ethnicity

• Type of Material: Article
• Authors: Badri Vardarajan, Vagelos College of Physicians and Surgeons; Vrinda Kalia, Columbia University; Jennifer Manly, Vagelos College of Physicians and Surgeons; Adam Brickman, Vagelos College of Physicians and Surgeons; Dolly Reyes-Dumeyer, Vagelos College of Physicians and Surgeons; Rafael Lantigua, New York Presbyterian Hospital; Iuliana Ionita-Laza, Columbia University Irving Medical Center; Dean Jones, Emory University; Gary Miller, Emory University; Richard Mayeux, Vagelos College of Physicians and Surgeons
• Language: English
• Date: 2020-01-01
• Publisher: Alzheimer's Association
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Alzheimer's Association.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/trc2.12025
• Title of Journal or Parent Work: Alzheimer's and Dementia: Translational Research and Clinical Interventions
• Volume: 6
• Issue: 1
• Start Page: e12025
• End Page: e12025
• Grant/Funding Information: WHICAP. Data collection and sharing for this project was supported by the Washington Heights‐Inwood Columbia Aging Project (WHICAP, PO1AG07232, R01AG037212, RF1AG054023, and R56AG063908) funded by the National Institute on Aging (NIA) and by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number UL1TR001873.; The metabolomics work was supported by U2C ES030163 and R01 ES023839.
• Keywords: multi‐ethnic; metabolite profile differences in Alzheimer's disease; metabolomics; Alzheimer's disease; APOE ε4; plasma
• Research Categories: Gerontology; Biology, Neuroscience; Environmental Sciences; Biology, Biostatistics

Abstract

Introduction: We investigated metabolites in plasma to capture systemic biochemical changes associated with Alzheimer's disease (AD). Methods: Metabolites in plasma were measured in 59 AD cases and 60 healthy participants of African American (AA), Caribbean Hispanic (CH), and non-Hispanic white (NHW) ancestry using untargeted liquid-chromatography–based ultra-high-resolution mass spectrometry. Metabolite differences between AD and healthy, ethnic groups and apolipoprotein E gene (APOE) ε4 status were analyzed. Untargeted network analysis identified pathways enriched in AD-associated metabolites. Results: A total of 5929 annotated metabolites were measured. Partial least squares discriminant analysis (PLS-DA) inferred that AD clustered separately from healthy controls (area under the curve [AUC] = 0.9816); discriminating pathways included glycerophospholipid, sphingolipid, and non-essential amino acid (alanine, aspartate, glutamate) metabolism. Metabolic features in AA clustered differently from CH and NHW (AUC = 0.9275), and differed between APOE ε4 carriers and non-carriers (AUC = 0.9972). Discussion: Metabolites, specifically lipids, were associated with AD, APOE ε4, and ethnic group. Metabolite profiling can identify perturbed AD pathways, but genetic and ancestral background need to be considered.