Fig. 1: Study design and workflow.

Seventeen blood fatty acid indicators were initially considered. Cox proportional hazard models were used to identify indicators closely associated with the risk of Alzheimer’s disease (AD). After Lasso regression (n = 7) and considering contribution degree in the nomogram (n = 2), a total of 8 indicators were finally included to construct the fatty acid risk score. The association of risk score with AD risk, cognition, hippocampus, and/or cerebrospinal fluid AD markers were tested in both UKB and ADNI cohorts. Mediation effects and interaction analyses by APOE ε4 were performed. Finally, proteomic analyses were conducted to elucidate the biological mechanisms of the interaction. “*” See e-Fig. 1 for details. FAS Fatty acid score.