APOE and Alzheimer disease: In 2020, Linard et al. [21] used a more robust gene-by-environment interaction study design to find that APOE4 carriers with recent HSV-1 reactivation (IgG+ and IgM+, or elevated IgG) developed AD at ~3× the rate of those merely infected with HSV-1 (IgG+); APOE4 noncarriers showed no such association.