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Schweickart, A.* ; Batra, R.* ; Huynh, K.* ; Blach, C.* ; Kueider-Paisley, A.* ; Reddy, J.S.* ; Bennett, D.A.* ; Meikle, P.J.* ; Zhang, B.* ; De Jager, P.L.* ; Heath, L.* ; Beck, J.* ; Scanlan, J.* ; Seyfried, N.T.* ; Dickson, D.W.* ; Ertekin-Taner, N.* ; Kaddurah-Daouk, R.* ; Arnold, M. ; Krumsiek, J.*

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

Alzheimers Dement. 22, 15:e71690 (2026)
Publ. Version/Full Text Research data DOI
Open Access Hybrid
Creative Commons Lizenzvertrag
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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Publication type Article: Journal article
Document type Scientific Article
Keywords Acetylcholine ; Alzheimer's Disease ; Amp‐ad Diverse Cohorts ; Apoe4 ; Braak Stage ; Brain Metabolomics ; Ceramide ; Dipeptides ; Dorsolateral Prefrontal Cortex ; Ethnoracial Differences ; Lipid Metabolism ; Metabolic Heterogeneity ; Multiethnic Cohort ; Neurodegeneration ; Population Health Disparities ; Post‐mortem Brain ; Precision Therapeutics ; Sphingolipid Metabolism ; Tau Pathology ; Tricarboxylic Acid Cycle; Alzheimers-disease; Prefrontal Cortex; Dementia; Recommendations; Discovery; Diagnosis
ISSN (print) / ISBN 1552-5260
e-ISSN 1552-5279
Journal Alzheimer's & Dementia
Quellenangaben Volume: 22, Issue: 10, Pages: 15, Article Number: e71690 Supplement: ,
Publisher Wiley
Publishing Place New York, NY [u.a.]
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Grants Alzheimer's Association
National Institute on Aging