Plasma proteomics of APOE genotype: age-specific analyses in UK population-based cohorts.
We characterised the effects of APOE ε4 and ε2 carriage on circulating plasma proteins in 42,642 UK Biobank participants across European, African, and South Asian ancestries. We identified 480 ε4-associated proteins and 351 ε2-associated proteins, including established neurodegeneration biomarkers (GFAP, NEFL) and proteins linked to Alzheimer’s disease risk loci (TREM2, CTSB, IDUA, SORT1, GRN). Many associations were age-dependent and detectable decades before typical Alzheimer’s disease diagnosis. Consistent changes in APOE, MENT, and PLA2G7 were observed across age groups, ancestries, and independent replication cohorts, highlighting potential early biomarkers and intervention targets.