APOE and Alzheimer disease: However, further investigation revealed that the increased decline in individuals with both APOE and other AD risk genes was driven primarily by an interaction between APOE and CD33. This is the first study we know of to suggest the possibility of an interaction between APOE ε4 and CD33 affecting cognitive function over time in the HRS data, although we acknowledge that the interaction was no longer significant once a correction for multiple comparisons was applied.