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Sex and APOE ε4 genotype modify the Alzheimer's disease serum metabolome.

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Arnold M,Nho K,Kueider-Paisley A,Massaro T,Huynh K,Brauner B,MahmoudianDehkordi S,Louie G,Moseley MA,Thompson JW,John-Williams LS,Tenenbaum JD,Blach C,Chang R,Brinton RD,Baillie R,Han X,Trojanowski JQ,Shaw LM,Martin

doi

10.1038/s41467-020-14959-w

subject

Has Abstract

pub_date

2020-03-02 00:00:00

pages

1148

issue

1

issn

2041-1723

pii

10.1038/s41467-020-14959-w

journal_volume

11

pub_type

杂志文章

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