Sex shapes plasma molecular signatures of dementia risk across APOE ε4 strata

Sex and APOE {varepsilon}4 influence dementia risk, but whether its molecular predictors differ across sex and APOE {varepsilon}4 strata remains unclear. We investigated plasma proteomic and metabolomic signatures predicting future dementia in 43,759 UK Biobank participants across four sex-by-APOE {varepsilon}4 groups. The association between APOE {varepsilon}4 carrier status and dementia differed by sex (interaction p = 0.027). Machine-learning models achieved higher discrimination in APOE {varepsilon}4 carriers (AUC 0.85-0.90) than non-carriers (AUC 0.74-0.76), with the highest performance i

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