Document Type

Journal Article

Publication Title

Nature Communications

Publisher

Nature Research

School

School of Medical and Health Sciences

RAS ID

30996

Comments

Arnold, M., Nho, K., Kueider-Paisley, A., Massaro, T., Huynh, K., Brauner, B., ... Kastenmuller, G. (2020). Sex and APOE ε4 genotype modify the Alzheimer’s disease serum metabolome. Nature Communications, 11, Article 1148. https://doi.org/10.1038/s41467-020-14959-w

Abstract

Late-onset Alzheimer’s disease (AD) can, in part, be considered a metabolic disease. Besides age, female sex and APOE ε4 genotype represent strong risk factors for AD that also give rise to large metabolic differences. We systematically investigated group-specific metabolic alterations by conducting stratified association analyses of 139 serum metabolites in 1,517 individuals from the AD Neuroimaging Initiative with AD biomarkers. We observed substantial sex differences in effects of 15 metabolites with partially overlapping differences for APOE ε4 status groups. Several group-specific metabolic alterations were not observed in unstratified analyses using sex and APOE ε4 as covariates. Combined stratification revealed further subgroup-specific metabolic effects limited to APOE ε4+ females. The observed metabolic alterations suggest that females experience greater impairment of mitochondrial energy production than males. Dissecting metabolic heterogeneity in AD pathogenesis can therefore enable grading the biomedical relevance for specific pathways within specific subgroups, guiding the way to personalized medicine.

DOI

10.1038/s41467-020-14959-w

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Research Themes

Health

Priority Areas

Neuroscience and neurorehabilitation

Share

 
COinS