Sphingolipid and ceramide associations with tau pathology vary across diverse ethnoracial groups in postmortem brain tissue
Year: 2026
Type: article
Study design: Observational Study
Abstract: INTRODUCTION: Metabolic dysregulation is a hallmark of Alzheimer's disease (AD), with numerous studies characterizing metabolic pathways associated with AD onset and progression. A limitation of these studies has been a focus on non-Hispanic white participants. Despite evidence that AD prevalence, progression, and biomarkers differ across ethnoracial groups, it remains unclear whether previously identified metabolic dysregulation in AD brains generalizes across populations. METHODS: We analyzed metabolomics data from 547 postmortem brain tissue samples of Hispanic American, Non-Hispanic African American, and White subjects, providing the largest multiethnic AD brain cohort to date. A metabolome-wide association study examined how relationships between metabolite abundance and AD neuropathology varied by ethnoracial group. RESULTS: Forty-eight metabolites exhibited significant heterogeneity with tau pathology (Braak stage), with enrichment in tricarboxylic-acid-cycle intermediates and sphingolipid-ceramide pathway lipids, and with metabolite-tau associations driven predominantly by the Hispanic American and non-Hispanic White groups. DISCUSSION: These findings reveal ethnoracial-specific metabolic signatures of tau pathology and emphasize the need to evaluate emerging therapeutic targets across diverse groups.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.71690
Authors: Annalise Schweickart, Richa Batra, Kevin Huynh, Collette Blach, Alexandra Kueider-Paisley, Joseph S. Reddy, Gregory Klein, David A. Bennett, Peter J. Meikle, Bin Zhang, Philip L. De Jager, Laura Heath, Jaclyn Beck, Jo Scanlan, Nicholas T. Seyfried, Dennis W. Dickson, Nilüfer Ertekin-Taner, AMP-AD Diverse Cohorts Working Group, Rima Kaddurah-Daouk, Matthias Arnold, Jan Krumsiek
Institutions: Buck Institute for Research on Aging, Weill Cornell Medicine, Baker Heart and Diabetes Institute, La Trobe University, Duke University, Mayo Clinic in Florida, Rush University Medical Center, Icahn School of Medicine at Mount Sinai, Columbia University Irving Medical Center, Sage Bionetworks, Emory University, Helmholtz Munich, Institute of Computational Biology
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,200
Awards: Integrative translational discovery of vascular risk factors in aging and dementia, G2520261784, The Role of Chemical Exposures in Alzheimer's Disease (AD) and its Trajectory, Integrative Network Biology Approaches to Identify, Characterize and Validate Molecular Subtypes in Alzheimer's Disease, G3002044485, Metabolic Trajectories of Alzheimer’s Disease Progression, Alzheimer's Gut Microbiome Project, Understanding the molecular mechanisms that contribute to neuropsychiatric symptoms in Alzheimer Disease, AMP-AD Brain Proteomic Network Enhancement, Validation, and Translation into CSF Biomarkers, Metabolomic Signatures for Disease Sub-classification and Target Prioritization in AMP-AD, Multi-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targets, TargetAD: A systems multi-omics approach to drug repositioning in Alzheimer's disease, A Systems Approach to Targeting Innate Immunity in AD, Harnessing Molecular Networks of Resilience for Therapeutic Discoveries in AD, G8203386035, Blood-Based Biomarkers of Vascular (Dys)function in Alzheimer's Disease, The AD Knowledge Portal Data Coordination Center, Metabolic age to define influences of the lipidome on brain aging in Alzheimer's disease, Mayo Alzheimer's Disease Research Center, Centrally-linked longitudinal peripheral biomarkers of AD in multi-ethnic populations, Training in Basic Research on Aging and Age-Related Disease
OpenAlex ID: W7221625308