Peer-reviewedCC BY-NCAlzheimer's & dementia : the journal of the Alzheimer's Association
Sphingolipid and ceramide associations with tau pathology vary across diverse ethnoracial groups in postmortem brain tissue.
14 affiliations
- 1Department of Systems and Computational Biomedicine, Weill Cornell Medicine, New York, New York, USA.
- 2Buck Institute for Research on Aging, Novato, California, USA.
- 3Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
- 4Baker Department of Cardiovascular Research Translation and Implementation, La Trobe University, Bundoora, Victoria, Australia.
- 5Department of Psychiatry and Behavioral Sciences, Duke Institute for Brain Sciences and Department of Medicine, Duke University, Durham, North Carolina, USA.
- 6Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
- 7Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
- 8Department of Genetics and Genomic Sciences, Mount Sinai Center for Transformative Disease Modeling, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
- 9Center for Translational and Computational Neuroimmunology, Department of Neurology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, New York, USA.
- 10Sage Bionetworks, Seattle, Washington, USA.
- 11Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA.
- 12Department of Biochemistry, Emory University, Atlanta, Georgia, USA.
- 13Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
- 14Institute of Computational Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
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.
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BibTeX
@article{schweickart2026sphingolipid,
title = {{Sphingolipid and ceramide associations with tau pathology vary across diverse ethnoracial groups in postmortem brain tissue.}},
author = {Annalise Schweickart and Richa Batra and Kevin Huynh and Collette Blach and Alexandra Kueider-Paisley and Joseph S Reddy and David A Bennett and Peter J Meikle and Bin Zhang and Philip L De Jager and Laura Heath and Jaclyn Beck and Jo Scanlan and Nicholas T Seyfried and Dennis W Dickson and Nilüfer Ertekin-Taner and Alzheimer's Disease Metabolomics Consortium and Rima Kaddurah-Daouk and Matthias Arnold and Jan Krumsiek},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2026},
month = oct,
doi = {10.1002/alz.71690},
url = {https://europepmc.org/article/MED/42869853},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Sphingolipid and ceramide associations with tau pathology vary across diverse ethnoracial groups in postmortem brain tissue.
AU - Annalise Schweickart
AU - Richa Batra
AU - Kevin Huynh
AU - Collette Blach
AU - Alexandra Kueider-Paisley
AU - Joseph S Reddy
AU - David A Bennett
AU - Peter J Meikle
AU - Bin Zhang
AU - Philip L De Jager
AU - Laura Heath
AU - Jaclyn Beck
AU - Jo Scanlan
AU - Nicholas T Seyfried
AU - Dennis W Dickson
AU - Nilüfer Ertekin-Taner
AU - Alzheimer's Disease Metabolomics Consortium
AU - Rima Kaddurah-Daouk
AU - Matthias Arnold
AU - Jan Krumsiek
PY - 2026
DA - 2026/10/01
JO - Alzheimer's & dementia : the journal of the Alzheimer's Association
DO - 10.1002/alz.71690
UR - https://europepmc.org/article/MED/42869853
AB - 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.
SN - 1552-5260
SN - 1552-5279
ER -