Apolipoprotein E4 (APOE-ε4), the strongest common genetic risk factor for Alzheimer’s disease (AD), contributes to worse cognition in older adults. However, many APOE-ε4 carriers remain cognitively normal throughout life, suggesting that neuroprotective factors may be present in these individuals. In this study, we leverage whole-blood RNA sequencing (RNAseq) from 324 older adults to identify genetic modifiers of APOE-ε4 effects on cognition. Expression of RNASE6 interacted with APOE-ε4 status (p = 4.35 × 10