However, the possibility that APOE4 may also affect the cognitive and pathological presentation of AD deserves significant attention, as this possibility may elucidate differing pathogenic mechanisms between APOE4+ vs. APOE4− AD patients, both before and after disease onset, and may have important implications for how we should therapeutically treat APOE4+ vs. APOE4− AD patients. This evidence concerns the gene APOE and Alzheimer disease.