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Sphingolipid and ceramide associations with tau pathology vary across diverse ethnoracial groups in postmortem brain tissue.

Created on 14 Oct 2026

Authors

Annalise Schweickart, Richa Batra, Kevin Huynh, Collette Blach, Alexandra Kueider-Paisley, Joseph S Reddy, 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, Alzheimer's Disease Metabolomics Consortium, Rima Kaddurah-Daouk, Matthias Arnold, Jan Krumsiek

Published in

Alzheimer's & dementia : the journal of the Alzheimer's Association. Volume 22. Issue 10. Pages e71690.

Abstract

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.
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.
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.
These findings reveal ethnoracial-specific metabolic signatures of tau pathology and emphasize the need to evaluate emerging therapeutic targets across diverse groups.

PMID:
42869853
Bibliographic data and abstract were imported from PubMed on 14 Oct 2026.

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